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Sample records for alpha tau k5

  1. The Atmospheric Dynamics of Alpha Tau (K5 III) -- Clues to Understanding the Magnetic Dynamo

    NASA Technical Reports Server (NTRS)

    Carpenter Kenneth G.

    2008-01-01

    Using HST/GHRS, HST/STIS and FUSE archival data for (alpha) Tau and the CHIANTI spectroscopic code, we have derived line shifts, volumetric emission measures, and plasma density estimates, and calculated filling factors for a number of UV lines forming between 10,000 K and 300,000 K in the outer atmosphere of this red giant star. The data suggest the presence of low-temperature extended regions and high-temperature compact regions, associated with magnetically open and closed structures in the stellar atmosphere, respectively. The signatures of UV lines from Alpha Tau can be consistently understood via a model of upward-traveling Alfven waves in a gravitationally stratified atmosphere. These wakes cause non-thermal broadening in UV lines due to unresolved wave motions and downward plasma motions in compact magnetic loops heated by resonant .4lf\\en wave heating. We discuss implications of this interpretation for understanding the nature of magnetic dynamos operating in late-type giants.

  2. The Atmospheric Dynamics of alpha Tau (K5 III) - Clues to Understanding the Magnetic Dynamo in Late-Type Giant Stars

    NASA Technical Reports Server (NTRS)

    Carpenter, Kenneth G.; Airapetian, Vladimir

    2008-01-01

    Using HST/GHRS, HST/STIS and FUSE archival data for alpha Tau and the CHIANTI spectroscopic code, we have derived line shifts, volumetric emission measures, and plasma density estimates, and calculated filling factors for a number of UV lines forming between 10,000 K and 300,000 K in the outer atmosphere of this red giant star. The data suggest the presence of low-temperature extended regions and high-temperature compact regions, associated with magnetically open and closed structures in the stellar atmosphere, respectively. The signatures of UV lines from alpha Tau can be consistently understood via a model of upward-traveling Alfven waves in a gravitationally stratified atmosphere. These waves cause non-thermal broadening in UV lines due to unresolved wave motions and downward plasma motions in compact magnetic loops heated by resonant Alfven wave heating.

  3. The Atmospheric Dynamics of Alpha Tau (K5 III) - Clues to Understanding the Magnetic Dynamo in Late-Type Giant Stars

    NASA Technical Reports Server (NTRS)

    Carpenter, Kenneth G.; Airapetian, Vladimir

    2008-01-01

    Using HST/GHRS, HST/STIS and FUSE archival data for a Tau and the CHIANTI spectroscopic code, we have derived line shifts, volumetric emission measures, and plasma density estimates, and calculated filling factors for a number of UV lines forming between 10,000 K and 300,000 K in the outer atmosphere of this red giant star. The data suggest the presence of low-temperature extended regions and high-temperature compact regions, associated with magnetically open and closed structures in the stellar atmosphere, respectively. The signatures of UV lines from a Tau can be consistently understood via a model of upward-traveling Alfv6n waves in a gravitationally stratified atmosphere. These waves cause nonthermal broadening in UV lines due to unresolved wave motions and downward plasma motions in compact magnetic loops heated by resonant Alfven wave heating.

  4. Far-Infrared and Millimeter Continuum Studies of K-Giants: Alpha Boo and Alpha Tau

    NASA Technical Reports Server (NTRS)

    Cohen, Martin; Carbon, Duane F.; Welch, William J.; Lim, Tanya; Forster, James R.; Goorvitch, David; Thigpen, William (Technical Monitor)

    2002-01-01

    We have imaged two normal, non-coronal, infrared-bright K-giants, alpha Boo and alpha Tau, in the 1.4-millimeter and 2.8-millimeter continuum using BIMA. These stars have been used as important absolute calibrators for several infrared satellites. Our goals are: (1) to probe the structure of their upper photospheres; (2) to establish whether these stars radiate as simple photospheres or possess long-wavelength chromospheres; and (3) to make a connection between millimeter-wave and far-infrared absolute flux calibrations. To accomplish these goals we also present ISO Long Wavelength Spectrometer (LWS) measurements of both these K-giants. The far-infrared and millimeter continuum radiation is produced in the vicinity of the temperature minimum in a Boo and a Tau, offering a direct test of the model photospheres and chromospheres for these two cool giants. We find that current photospheric models predict fluxes in reasonable agreement with those observed for those wavelengths which sample the upper photosphere, namely less than or equal to 170 micrometers in alpha Tau and less than or equal to 125 micrometers in alpha Boo. It is possible that alpha Tau is still radiative as far as 0.9 - 1.4 millimeters. We detect chromospheric radiation from both stars by 2.8 millimeters (by 1.4 millimeters in alpha Boo), and are able to establish useful bounds on the location of the temperature minimum. An attempt to interpret the chromospheric fluxes using the two-component "bifurcation model" proposed by Wiedemann et al. (1994) appears to lead to a significant contradiction.

  5. Short-Term Chromospheric Variability in alpha Tauri (K5 III): Results from IUE Time Series Observations

    NASA Technical Reports Server (NTRS)

    Cuntz, Manfred; Deeney, Bryan D.; Brown, Alexander; Stencel, Robert E.

    1996-01-01

    We evaluate time series observations of chromospheric lines (Mg II, Mg I, and C II) for the K giant alpha Tau obtained using the IUE LWP camera at high dispersion. These observations cover a time span of about 2 weeks in 1994 February-March and were designed to resolve variations occurring within hours, days, and weeks. We consider the observational results in relation to theoretical acoustic heating models, motivated by the fact that alpha Tau may exhibit a basal (i.e., minimum) level of chromospheric activity. The data reveal flux variations between the extremes of 8% in Mg II h+k and 15% in each emission component. These variations occur on timescales as short as 8 hr but not on timescales longer than approx.3 days. For the h and k components, flux variations occurring on a timescale as short as 1.5 hr are also found. These changes are often not correlated (and are sometimes even anticorrelated), leading to remarkable differences in the h/k ratios. We argue that these results are consistent with the presence of strong acoustic shocks, which can lead to variable Mg II line emission when only a small number of strong shocks are propagating through the atmosphere. We deduce the electron density in the C II lambda 2325 line formation region to be log(base e) of N. approx. equals 9.0, in agreement with previous studies. Our data provide evidence that the Mg II basal flux limit for K giants might be a factor of 4 higher than suggested by Rutten et al.

  6. On the Behavior of the Effective QCD Coupling {alpha}{sub {tau}}(s)at Low Scales

    SciTech Connect

    Brodsky, Stanley J.

    2002-12-11

    The hadronic decays of the {tau} lepton can be used to determine the effective charge {alpha}{tau}(m{sub {tau}{prime}}{sup 2}) for a hypothetical {tau}-lepton with mass in the range 0 < m{sub {tau}{prime}} < m{sub {tau}}. This definition provides a fundamental definition of the QCD coupling at low mass scales. We study the behavior of {alpha}{sub {tau}} at low mass scales directly from first principles and without any renormalization-scheme dependence by looking at the experimental data from the OPAL Collaboration. The results are consistent with the freezing of the physical coupling at mass scales s = m{sub {tau}{prime}}{sup 2} of order 1 GeV{sup 2} with a magnitude {alpha}{sub {tau}} {approx} 0.9 {+-} 0.1.

  7. MicroRNA-138 promotes tau phosphorylation by targeting retinoic acid receptor alpha.

    PubMed

    Wang, Xiong; Tan, Lu; Lu, Yanjun; Peng, Jing; Zhu, Yaowu; Zhang, Yadong; Sun, Ziyong

    2015-03-12

    Alzheimer's disease (AD) is a progressive neurodegenerative dementia characterized by Aβ deposition and neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau. Emerging evidence shows that microRNAs (miRNAs) contribute to the pathogenesis of AD. Herein, we investigated the role of miR-138, a brain enriched miRNA, which is increased in AD patients. We found that miR-138 is increased in AD models, including N2a/APP and HEK293/tau cell lines. Overexpression of miR-138 activates glycogen synthase kinase-3β (GSK-3β), and increases tau phosphorylation in HEK293/tau cells. Furthermore, we confirm that retinoic acid receptor alpha (RARA) is a direct target of miR-138, and supplement of RARA substantially suppresses GSK-3β activity, and reduces tau phosphorylation induced by miR-138. In conclusion, our data suggest that miR-138 promotes tau phosphorylation by targeting the RARA/GSK-3β pathway. PMID:25680531

  8. Soluble amyloid precursor protein alpha inhibits tau phosphorylation through modulation of GSK3β signaling pathway.

    PubMed

    Deng, Juan; Habib, Ahsan; Obregon, Demian F; Barger, Steven W; Giunta, Brian; Wang, Yan-Jiang; Hou, Huayan; Sawmiller, Darrell; Tan, Jun

    2015-11-01

    We recently found that sAPPα decreases amyloid-beta generation by directly associating with β-site amyloid precursor protein (APP)-converting enzyme 1 (BACE1), thereby modulating APP processing. Because inhibition of BACE1 decreases glycogen synthase kinase 3 beta (GSK3β)-mediated Alzheimer's disease (AD)-like tau phosphorylation in AD patient-derived neurons, we determined whether sAPPα also reduces GSK3β-mediated tau phosphorylation. We initially found increased levels of inhibitory phosphorylation of GSK3β (Ser9) in primary neurons from sAPPα over-expressing mice. Further, recombinant human sAPPα evoked the same phenomenon in SH-SY5Y cells. Further, in SH-SY5Y cells over-expressing BACE1, and HeLa cells over-expressing human tau, sAPPα reduced GSK3β activity and tau phosphorylation. Importantly, the reductions in GSK3β activity and tau phosphorylation elicited by sAPPα were prevented by BACE1 but not γ-secretase inhibition. In accord, AD mice over-expressing human sAPPα had less GSK3β activity and tau phosphorylation compared with controls. These results implicate a direct relationship between APP β-processing and GSK3β-mediated tau phosphorylation and further define the central role of sAPPα in APP autoregulation and AD pathogenesis. PMID:26342176

  9. Alpha 1-Antichymotrypsin, an Inflammatory Protein Overexpressed in the Brains of Patients with Alzheimer's Disease, Induces Tau Hyperphosphorylation through c-Jun N-Terminal Kinase Activation.

    PubMed

    Tyagi, Ethika; Fiorelli, Tina; Norden, Michelle; Padmanabhan, Jaya

    2013-01-01

    The association of inflammatory proteins with neuritic plaques in the brains of Alzheimer's disease (AD) patients has led to the hypothesis that inflammation plays a pivotal role in the development of pathology in AD. Earlier studies have shown that alpha 1-antichymotrypsin (ACT) enhances amyloid beta fibrillization and accelerated plaque formation in APP transgenic mice. Later studies from our laboratory have shown that purified ACT induces tau hyperphosphorylation and degeneration in neurons. In order to understand the mechanisms by which inflammatory proteins enhance tau hyperphosphorylation, we injected interleukin-1 β (IL-1 β ) intracerebroventricularly into mice expressing human ACT, human tau, or both transgenes. It was found that the hyperphosphorylation of tau in ACT and ACT/htau mice after IL-1 β injection correlated with increased phosphorylation of c-Jun N-terminal kinase (JNK). We verified the involvement of JNK in ACT-induced tau phosphorylation by utilizing JNK inhibitors in cultured primary neurons treated with ACT, and we found that the inhibitor showed complete prevention of ACT-induced tau phosphorylation. These results indicate that JNK is one of the major kinases involved in the ACT-mediated tau hyperphosphorylation and suggest that inhibitors of this kinase may protect against inflammation-induced tau hyperphosphorylation and neurodegeneration associated with AD. PMID:24175110

  10. Persistent Sub-Yearly Chromospheric Variations in Lower Main-Sequence Stars: Tau Booe and alpha Com

    NASA Technical Reports Server (NTRS)

    Maulik, Davesh; Donahue, Robert A.; Baliunas, Sallie L.

    1997-01-01

    The recent discoveries of extrasolar planetary systems around lower main-sequence stars such as tau Booe (HD 120136) has prompted further investigation into their stellar activity. A cursory analysis of tau Booe for cyclic chromospheric activity, based on its 30-yr record of Ca 2 H and K fluxes obtained as part of the HK Project from Mount Wilson Observatory, finds an intermediate, sub-yearly period (approximately 117 d) in chromospheric activity in addition to, and separate from, both its rotation (3.3 d) and long-term variability. As a persistent subyearly period in surface magnetic activity is unprecedented, we investigate this apparent anomaly further by examining chromospheric activity levels of other stars with similar mass, searching for variability in chromospheric activity with periods of less than one year, but longer than measured or predicted rotation. An examination of the time series of 40 mid-to-late F dwarfs yielded one other star for further analysis: alpha Com (HD 114378, P approximately 132 d). The variations for these two stars were checked for persistence and coherence. Based on these determinations, we eliminate the possibilities of rotation, long-term activity cycle, and the evolution of active regions as the cause of this variation in both stars. In particular, for tau Booe we infer that the phenomenon may be chromospheric in origin; however, beyond this, it is difficult to identify anything further regarding the cause of the activity variations, or even whether the observed modulation in the two stars have the same origin.

  11. HST/COS SPECTRA OF DF Tau AND V4046 Sgr: FIRST DETECTION OF MOLECULAR HYDROGEN ABSORPTION AGAINST THE Ly{alpha} EMISSION LINE

    SciTech Connect

    Yang Hao; Linsky, Jeffrey L.; France, Kevin E-mail: jlinsky@jilau1.colorado.edu

    2011-03-20

    We report the first detection of molecular hydrogen (H{sub 2}) absorption in the Ly{alpha} emission line profiles of two classical T Tauri stars (CTTSs), DF Tau and V4046 Sgr, observed by the Hubble Space Telescope/Cosmic Origins Spectrograph. This absorption is the energy source for many of the Lyman-band H{sub 2} fluorescent lines commonly seen in the far-ultraviolet spectra of CTTSs. We find that the absorbed energy in the H{sub 2} pumping transitions from a portion of the Ly{alpha} line significantly differ from the amount of energy in the resulting fluorescent emission. By assuming additional absorption in the H I Ly{alpha} profile along our light of sight, we can correct the H{sub 2} absorption/emission ratios so that they are close to unity. The required H I absorption for DF Tau is at a velocity close to the radial velocity of the star, consistent with H I absorption in the edge-on disk and interstellar medium. For V4046 Sgr, a nearly face-on system, the required absorption is between +100 km s{sup -1} and +290 km s{sup -1}, most likely resulting from H I gas in the accretion columns falling onto the star.

  12. Cerebrospinal Fluid Amyloid β1-42, Tau, and Alpha-Synuclein Predict the Heterogeneous Progression of Cognitive Dysfunction in Parkinson’s Disease

    PubMed Central

    Kang, Ju-Hee

    2016-01-01

    Parkinson’s disease (PD) is a neurodegenerative disease with heterogeneous pathological and clinical features. Cognitive dysfunction, a frequent non-motor complication, is a risk factor for poor prognosis and shows inter-individual variation in its progression. Of the clinical studies performed to identify biomarkers of PD progression, the Parkinson’s Progression Markers Initiative (PPMI) study is the largest study that enrolled drug-naïve and very early stage PD patients. The baseline characteristics of the PPMI cohort were recently published. The diagnostic utility of cerebrospinal fluid (CSF) biomarkers, including alpha-synuclein (α-syn), total tau, phosphorylated tau at Thr181, and amyloid β1-42, was not satisfactory. However, the baseline data on CSF biomarkers in the PPMI study suggested that the measurement of the CSF biomarkers enables the prediction of future cognitive decline in PD patients, which was consistent with previous studies. To prove the hypothesis that the interaction between Alzheimer’s pathology and α-syn pathology is important to the progression of cognitive dysfunction in PD, longitudinal observational studies must be followed. In this review, the neuropathological nature of heterogeneous cognitive decline in PD is briefly discussed, followed by a summarized interpretation of baseline CSF biomarkers derived from the data in the PPMI study. The combination of clinical, biochemical, genetic and imaging biomarkers of PD constitutes a feasible strategy to predict the heterogeneous progression of PD. PMID:27240810

  13. Photometric and spectroscopic monitoring of AA Tau, DN Tau, UX Tau A, T Tau, RY Tau, Lk Ca 4, and Lk Ca 7

    NASA Technical Reports Server (NTRS)

    Vrba, F. J.; Chugainov, P. F.; Weaver, W. B.; Stauffer, J. S.

    1993-01-01

    We report the results of a UBVRI photometric monitoring campaign for three classical T Tauri stars (AA Tau, DN Tau, and UX Tau A) and two weak emission line T Tauri stars (Lk Ca 4 and Lk Ca 7). Observations were obtained at three sites during a core observing period spanning UT 1985 October 14 through UT 1985 December 25, with additional observations continuing until UT 1986 April 6. Concurrent spectrophotometric observations were obtained for all main program stars except Lk Ca 7 and additionally for T Tau, RW Aur, and RY Tau. Periodic photometric variability, assumed to be the stars' rotation periods, were found for AA Tau, DN Tau, Lk Ca 4, and Lk Ca 7, respectively, as 8.2, 6.3, 3.4, and 5.7 days. Several U-filter flares were observed for Lk Ca 4 and Lk Ca 7, which are strongly concentrated toward phases of minimum light. Correlations are found between H-alpha line strengths and V magnitudes for AA Tau and RY Tau. An analysis of absolute color variations of classical T Tauri stars confirms that hot spots are the predominant cause of these stars' variability. Our overall results are consistent with earlier findings that long-lived cool spots are responsible for most of the variability found for weak-emission T Tauri stars, while temporal hot spots are primarily responsible for the observed variability found in classical T Tauri stars.

  14. Reproductive and developmental toxicity studies on catena-(S)-[mu-[N alpha-(3-aminopropionyl) histidinato(2-)-N1,N2,O:N tau]-zinc].

    PubMed

    Matsuda, K; Nishi, N; Hiramatsu, Y; Shimizu, M; Ohta, T; Kato, M

    1991-10-01

    To evaluate the effects of Z-103 (catena-(S)-[mu-[N alpha-(3-aminopropionyl) histidinato (2-)-N1,N2,O:N tau]-zinc], CAS 107667-60-7) on the reproductive performance of male and female rats, the general toxicity of dams, and the development, physical growth and reproductive performance of the next generation, Z-103 was administered to rats prior to, and in the early stages of pregnancy, during the period of fetal organogenesis, and during the perinatal and lactation periods, and to rabbits during the period of fetal organogenesis at the appropriate doses for each study. At the administration of Z-103 prior to and in the early stages of pregnancy in rats, no dose-related abnormalities were observed in the reproductive performance of either sex. Furthermore, there were no death or evidence of teratogenicity or repressive effect on growth in fetuses. Administration of Z-103 during the period of fetal organogenesis in rats affected the growth of embryos and fetuses at 1200 mg/kg. At 600 mg/kg or less, however, there were no death, teratogenicity or repressive effect on growth in fetuses, and furthermore, no dose-related abnormalities were observed in growth, physical development, behavior and reproductive performance in offspring. Administration of Z-103 during the period of fetal organogenesis in rabbits caused a decrease in the number of live fetuses at 300 mg/kg suggesting that 300 mg/kg of Z-103 may have a lethal effect on fetuses. There were, however, neither teratogenicity nor any repressive effect on the growth of fetuses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1799381

  15. Balmer decrements of T Tau stars

    NASA Astrophysics Data System (ADS)

    Katysheva, N. A.

    1981-04-01

    The relative intensities of Balmer lines calculated on the basis of Sobolev's probability method (1947) and the observed decrements of T Tau stars in the catalog of Cohen and Kuhi (1979) are compared with spectral classes between K5 and M5. For the group of stars, G5-K5, studied by Grinin (1980), emission was found to be predominantly of an envelope type, with less of a part played by chromospheric radiation. In K5-M5 stars, however, the envelope makes a smaller contribution to the total radiation, and most of the emission arises in the dense gas at the surface of the star. A comparison of the Balmer decrements of T Tau stars of different spectral classes and flare stars shows that in a transition to stars of lower luminosity, the role of chromospheric radiation increases.

  16. AMP-activated protein kinase modulates tau phosphorylation and tau pathology in vivo.

    PubMed

    Domise, Manon; Didier, Sébastien; Marinangeli, Claudia; Zhao, Haitian; Chandakkar, Pallavi; Buée, Luc; Viollet, Benoit; Davies, Peter; Marambaud, Philippe; Vingtdeux, Valérie

    2016-01-01

    Neurofibrillary tangles (NFTs) are the pathological hallmark of neurodegenerative diseases commonly known as tauopathies. NFTs result from the intracellular aggregation of abnormally and hyperphosphorylated tau proteins. Tau functions, which include the regulation of microtubules dynamics, are dependent on its phosphorylation status. As a consequence, any changes in tau phosphorylation can have major impacts on synaptic plasticity and memory. Recently, it has been demonstrated that AMP-activated protein kinase (AMPK) was deregulated in the brain of Alzheimer's disease (AD) patients where it co-localized with phosphorylated tau in pre-tangle and tangle-bearing neurons. Besides, it was found that AMPK was a tau kinase in vitro. Here, we find that endogenous AMPK activation in mouse primary neurons induced an increase of tau phosphorylation at multiple sites, whereas AMPK inhibition led to a rapid decrease of tau phosphorylation. We further show that AMPK mice deficient for one of the catalytic alpha subunits displayed reduced endogenous tau phosphorylation. Finally, we found that AMPK deficiency reduced tau pathology in the PS19 mouse model of tauopathy. These results show that AMPK regulates tau phosphorylation in mouse primary neurons as well as in vivo, and thus suggest that AMPK could be a key player in the development of AD pathology. PMID:27230293

  17. AMP-activated protein kinase modulates tau phosphorylation and tau pathology in vivo

    PubMed Central

    Domise, Manon; Didier, Sébastien; Marinangeli, Claudia; Zhao, Haitian; Chandakkar, Pallavi; Buée, Luc; Viollet, Benoit; Davies, Peter; Marambaud, Philippe; Vingtdeux, Valérie

    2016-01-01

    Neurofibrillary tangles (NFTs) are the pathological hallmark of neurodegenerative diseases commonly known as tauopathies. NFTs result from the intracellular aggregation of abnormally and hyperphosphorylated tau proteins. Tau functions, which include the regulation of microtubules dynamics, are dependent on its phosphorylation status. As a consequence, any changes in tau phosphorylation can have major impacts on synaptic plasticity and memory. Recently, it has been demonstrated that AMP-activated protein kinase (AMPK) was deregulated in the brain of Alzheimer’s disease (AD) patients where it co-localized with phosphorylated tau in pre-tangle and tangle-bearing neurons. Besides, it was found that AMPK was a tau kinase in vitro. Here, we find that endogenous AMPK activation in mouse primary neurons induced an increase of tau phosphorylation at multiple sites, whereas AMPK inhibition led to a rapid decrease of tau phosphorylation. We further show that AMPK mice deficient for one of the catalytic alpha subunits displayed reduced endogenous tau phosphorylation. Finally, we found that AMPK deficiency reduced tau pathology in the PS19 mouse model of tauopathy. These results show that AMPK regulates tau phosphorylation in mouse primary neurons as well as in vivo, and thus suggest that AMPK could be a key player in the development of AD pathology. PMID:27230293

  18. Comparing Fit and Reliability Estimates of a Psychological Instrument Using Second-Order CFA, Bifactor, and Essentially Tau-Equivalent (Coefficient Alpha) Models via AMOS 22

    ERIC Educational Resources Information Center

    Black, Ryan A.; Yang, Yanyun; Beitra, Danette; McCaffrey, Stacey

    2015-01-01

    Estimation of composite reliability within a hierarchical modeling framework has recently become of particular interest given the growing recognition that the underlying assumptions of coefficient alpha are often untenable. Unfortunately, coefficient alpha remains the prominent estimate of reliability when estimating total scores from a scale with…

  19. Tau protein binds to pericentromeric DNA: a putative role for nuclear tau in nucleolar organization.

    PubMed

    Sjöberg, Marcela K; Shestakova, Elena; Mansuroglu, Zeyni; Maccioni, Ricardo B; Bonnefoy, Eliette

    2006-05-15

    The microtubule-associated tau protein participates in the organization and integrity of the neuronal cytoskeleton. A nuclear form of tau has been described in neuronal and non-neuronal cells, which displays a nucleolar localization during interphase but is associated with nucleolar-organizing regions in mitotic cells. In the present study, based on immunofluorescence, immuno-FISH and confocal microscopy, we show that nuclear tau is mainly present at the internal periphery of nucleoli, partially colocalizing with the nucleolar protein nucleolin and human AT-rich alpha-satellite DNA sequences organized as constitutive heterochromatin. By using gel retardation, we demonstrate that tau not only colocalizes with, but also specifically binds to, AT-rich satellite DNA sequences apparently through the recognition of AT-rich DNA stretches. Here we propose a functional role for nuclear tau in relation to the nucleolar organization and/or heterochromatinization of a portion of RNA genes. Since nuclear tau has also been found in neurons from patients with Alzheimer's disease (AD), aberrant nuclear tau could affect the nucleolar organization during the course of AD. We discuss nucleolar tau associated with AT-rich alpha-satellite DNA sequences as a potential molecular link between trisomy 21 and AD. PMID:16638814

  20. What Renders TAU Toxic

    PubMed Central

    Götz, Jürgen; Xia, Di; Leinenga, Gerhard; Chew, Yee Lian; Nicholas, Hannah R.

    2013-01-01

    TAU is a microtubule-associated protein that under pathological conditions such as Alzheimer’s disease (AD) forms insoluble, filamentous aggregates. When 20 years after TAU’s discovery the first TAU transgenic mouse models were established, one declared goal that was achieved was the modeling of authentic TAU aggregate formation in the form of neurofibrillary tangles. However, as we review here, it has become increasingly clear that TAU causes damage much before these filamentous aggregates develop. In fact, because TAU is a scaffolding protein, increased levels and an altered subcellular localization (due to an increased insolubility and impaired clearance) result in the interaction of TAU with cellular proteins with which it would otherwise either not interact or do so to a lesser degree, thereby impairing their physiological functions. We specifically discuss the non-axonal localization of TAU, the role phosphorylation has in TAU toxicity and how TAU impairs mitochondrial functions. A major emphasis is on what we have learned from the four available TAU knock-out models in mice, and the knock-out of the TAU/MAP2 homolog PTL-1 in worms. It has been proposed that in human pathological conditions such as AD, a rare toxic TAU species exists which needs to be specifically removed to abrogate TAU’s toxicity and restore neuronal functions. However, what is toxic in one context may not be in another, and simply reducing, but not fully abolishing TAU levels may be sufficient to abrogate TAU toxicity. PMID:23772223

  1. Pathways of tau fibrillization.

    PubMed

    Kuret, Jeff; Chirita, Carmen N; Congdon, Erin E; Kannanayakal, Theresa; Li, Guibin; Necula, Mihaela; Yin, Haishan; Zhong, Qi

    2005-01-01

    New methods for analyzing tau fibrillization have yielded insights into the biochemical transitions involved in the process. Here we review the parallels between the sequential progression of tau fibrillization observed macroscopically in Alzheimer's disease (AD) lesions and the pathway of tau aggregation observed in vitro with purified tau preparations. In addition, pharmacological agents for further dissection of fibrillization mechanism and lesion formation are discussed. PMID:15615636

  2. Voyager observations of Zeta Tau

    NASA Technical Reports Server (NTRS)

    Carone, T. E.; Polidan, R. S.

    1987-01-01

    Two Voyager observations of Zeta Tau, a well-known Be/shell star of spectral type B1 IVe and vsin(i) = 220 km/s, separated by 503 days are presented and discussed. The observations show that in the spectral region shortward of Lyman-alpha, the 950-1150 A flux increased by about 40 percent, while in the region longward of 1300 A the flux increased by about 30 percent. Changes in features at 975 A and at 1020 A also appear. The observed change in the continuum flux is probably associated with a change in the effective temperature of the underlying B star, though change in the ubiquitous Fe II lines cannot be ruled out as the cause. The line variations are consistent with IUE spectra of Zeta Tau taken during the same time period.

  3. Unraveling duality violations in hadronic tau decays

    SciTech Connect

    Cata, Oscar; Cata, Oscar; Golterman, Maarten; Peris, Santiago

    2008-03-03

    There are some indications from recent determinations of the strong coupling constant alpha_s and the gluon condensate that the Operator Product Expansion may not be accurate enough to describe non-perturbative effects in hadronic tau decays. This breakdown of the Operator Product Expansion is usually referred to as being due to"Duality Violations." With the help of a physically motivated model, we investigate these duality violations. Based on this model, we argue how they may introduce a non-negligible systematic error in the current analysis, which employs finite-energy sum rules with pinched weights. In particular, this systematic effect might affect the precision determination of alpha_s from tau decays. With a view to a possible future application to real data, we present an alternative method for determining the OPE coefficients that might help estimating, and possibly even reducing, this systematic error.

  4. Gene expression profiling of breast cancer patients treated with docetaxel, doxorubicin, and cyclophosphamide within the GEPARTRIO trial: HER-2, but not topoisomerase II alpha and microtubule-associated protein tau, is highly predictive of tumor response.

    PubMed

    Rody, A; Karn, T; Gätje, R; Ahr, A; Solbach, C; Kourtis, K; Munnes, M; Loibl, S; Kissler, S; Ruckhäberle, E; Holtrich, U; von Minckwitz, G; Kaufmann, M

    2007-02-01

    Gene expression analysis in breast cancer patients undergoing neoadjuvant chemotherapy is an interesting tool for identification of gene signatures and new markers to predict tumor response. However, the detection of predictive markers strongly depends on the drugs used in the specific therapeutic setting. There is growing evidence that topoisomerase II-alpha (TOPO IIalpha) is a marker for anthracycline-, and microtubule-associated protein tau (MAPT) for taxane sensitivity. HER-2 has been described as a marker of both anthracycline and taxane sensitivity. We performed gene expression profiling of 50 patients within the GEPARTRIO study, an anthracycline and taxane neoadjuvant chemotherapy trial. Here we investigate the predictive value of TOPO IIalpha, MAPT and HER-2 mRNA expression for pathological complete response (pCR) in this setting. Interestingly, HER-2 gene expression was strongly predictive of pCR (P=0.017) as well as overall response (P=0.037) and clinical complete response (cCR, P=0.050). In contrast, for both TOPO IIalpha and MAPT no correlation with pCR was observed in our sample group. PMID:17010609

  5. Heterotypic seeding of Tau fibrillization by pre-aggregated Abeta provides potent seeds for prion-like seeding and propagation of Tau-pathology in vivo.

    PubMed

    Vasconcelos, Bruno; Stancu, Ilie-Cosmin; Buist, Arjan; Bird, Matthew; Wang, Peng; Vanoosthuyse, Alexandre; Van Kolen, Kristof; Verheyen, An; Kienlen-Campard, Pascal; Octave, Jean-Noël; Baatsen, Peter; Moechars, Diederik; Dewachter, Ilse

    2016-04-01

    Genetic, clinical, histopathological and biomarker data strongly support Beta-amyloid (Aβ) induced spreading of Tau-pathology beyond entorhinal cortex (EC), as a crucial process in conversion from preclinical cognitively normal to Alzheimer's Disease (AD), while the underlying mechanism remains unclear. In vivo preclinical models have reproducibly recapitulated Aβ-induced Tau-pathology. Tau pathology was thereby also induced by aggregated Aβ, in functionally connected brain areas, reminiscent of a prion-like seeding process. In this work we demonstrate, that pre-aggregated Aβ can directly induce Tau fibrillization by cross-seeding, in a cell-free assay, comparable to that demonstrated before for alpha-synuclein and Tau. We furthermore demonstrate, in a well-characterized cellular Tau-aggregation assay that Aβ-seeds cross-seeded Tau-pathology and strongly catalyzed pre-existing Tau-aggregation, reminiscent of the pathogenetic process in AD. Finally, we demonstrate that heterotypic seeded Tau by pre-aggregated Aβ provides efficient seeds for induction and propagation of Tau-pathology in vivo. Prion-like, heterotypic seeding of Tau fibrillization by Aβ, providing potent seeds for propagating Tau pathology in vivo, as demonstrated here, provides a compelling molecular mechanism for Aβ-induced propagation of Tau-pathology, beyond regions with pre-existing Tau-pathology (entorhinal cortex/locus coeruleus). Cross-seeding along functional connections could thereby resolve the initial spatial dissociation between amyloid- and Tau-pathology, and preferential propagation of Tau-pathology in regions with pre-existing 'silent' Tau-pathology, by conversion of a 'silent' Tau pathology to a 'spreading' Tau-pathology, observed in AD. PMID:26739002

  6. Untangling tau imaging.

    PubMed

    Villemagne, Victor L; Okamura, Nobuyuki; Rowe, Christopher C

    2016-01-01

    In vivo imaging of tau deposits is providing a better understanding of the temporal and spatial tau deposition in the brain, allowing a more comprehensive insight into the causes, diagnoses, and potentially treatment of tauopathies such as Alzheimer's disease, progressive supranuclear palsy, corticobasal syndrome, chronic traumatic encephalopathy, and some variants of frontotemporal lobar degeneration. The assessment of tau deposition in the brain over time will allow a deeper understanding of the relationship between tau and other variables such as cognition, genotype, and neurodegeneration, as well as assessing the role tau plays in ageing. Preliminary human studies suggest that tau imaging could also be used as a diagnostic, prognostic, and theranostic biomarker, as well as a surrogate marker for target engagement, patient recruitment, and efficacy monitoring for disease-specific therapeutic trials. PMID:27489878

  7. Tau polarisation at LEP

    NASA Astrophysics Data System (ADS)

    Alemany, Ricard

    1999-04-01

    The measurements of the tau polarisation at LEP I are reviewed. Special emphasis is given to the new preliminary results presented at this conference. The ALEPH collaboration has studied the polarisation as a function of the polar angle using a new method based on the tau direction reconstruction and fully exploiting the angular correlations. A second traditional approach, based on the single tau decays has been also developed. The DELPHI collaboration has also studied the full data sample using an individual tau decay method and an inclusive hadronic selection. The results from the four experiments are presented with discussion of the compatibility among the methods and experiments.

  8. Study on the metabolic fate of catena-(S)-[mu-N alpha-(3-aminopropionyl)histidinato(2-)-N1,N2,O:N tau]-zinc]. 3rd communication: transfer into fetus and milk in rats.

    PubMed

    Toyama, S; Furuta, S; Miwa, M; Suzuki, M; Sano, H; Matsuda, K

    1991-09-01

    Studies on the transfer into the fetus and the milk were performed after administration of 14C-Z-103 and 65Zn-Z-103 (catena-(S)-[mu-[N alpha-(3-aminopropionyl)histidinato(2-)-N1,N2,O:N tau]- zinc], CAS 107667-60-7) to rats. After oral administration of 14C-Z-103 to pregnant rats, the transfer of radioactivity to the fetus was studied by means of whole body autoradiography (ARG) and measurement of radioactivity in the fetus. The concentration of radioactivity in the fetus was approximately the same as those in the blood and the placenta of the maternal animal. The transfer of radioactivity into the milk was demonstrated after administration of 14C-Z-103 to lactating rats. Radioactivity in the fetus and milk are considered to be due to metabolites of L-carnosine of Z-103, such as amino acid or protein. The distribution of radioactivity in the fetus was also observed after administration of 65Zn-Z-103 to pregnant rats. However, after administration of non-radioactive Z-103 to pregnant rats, the zinc level in the fetus was found to be almost the same level as that in the fetus of the untreated rats. The transfer of radioactivity to the milk was studied after administration of 65Zn-Z-103 to the lactating rats, and it was seen that the concentration of radioactive zinc in the milk was much lower than the endogenous level of zinc in the milk at any of the time points investigated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1796929

  9. Measurement of the tau lifetime

    SciTech Connect

    Jaros, J.A.

    1982-10-01

    If the tau lepton couples to the charged weak current with universal strength, its lifetime can be expressed in terms of the muon's lifetime, the ratio of the masses of the muon and the tau, and the tau's branching ratio into e anti nu/sub e/ nu/sub tau/ as tau/sub tau/ = tau/sub ..mu../ (m/sub ..mu..//m/sub tau/)/sup 5/ B(tau ..-->.. e anti nu/sub e/nu/sub tau/) = 2.8 +- 0.2 x 10/sup -13/ s. This paper describes the measurement of the tau lifetime made by the Mark II collaboration, using a new high precision drift chamber in contunction with the Mark II detector at PEP. The results of other tau lifetime measurements are summarized.

  10. CHIP and Hsp70 regulate tau ubiquitination, degradation and aggregation.

    PubMed

    Petrucelli, Leonard; Dickson, Dennis; Kehoe, Kathryn; Taylor, Julie; Snyder, Heather; Grover, Andrew; De Lucia, Michael; McGowan, Eileen; Lewis, Jada; Prihar, Guy; Kim, Jungsu; Dillmann, Wolfgang H; Browne, Susan E; Hall, Alexis; Voellmy, Richard; Tsuboi, Yoshio; Dawson, Ted M; Wolozin, Benjamin; Hardy, John; Hutton, Mike

    2004-04-01

    Molecular chaperones, ubiquitin ligases and proteasome impairment have been implicated in several neurodegenerative diseases, including Alzheimer's and Parkinson's disease, which are characterized by accumulation of abnormal protein aggregates (e.g. tau and alpha-synuclein respectively). Here we report that CHIP, an ubiquitin ligase that interacts directly with Hsp70/90, induces ubiquitination of the microtubule associated protein, tau. CHIP also increases tau aggregation. Consistent with this observation, diverse of tau lesions in human postmortem tissue were found to be immunopositive for CHIP. Conversely, induction of Hsp70 through treatment with either geldanamycin or heat shock factor 1 leads to a decrease in tau steady-state levels and a selective reduction in detergent insoluble tau. Furthermore, 30-month-old mice overexpressing inducible Hsp70 show a significant reduction in tau levels. Together these data demonstrate that the Hsp70/CHIP chaperone system plays an important role in the regulation of tau turnover and the selective elimination of abnormal tau species. Hsp70/CHIP may therefore play an important role in the pathogenesis of tauopathies and also represents a potential therapeutic target. PMID:14962978

  11. Pfaffian and Determinantal Tau Functions

    NASA Astrophysics Data System (ADS)

    van de Leur, Johan W.; Orlov, Alexander Yu.

    2015-11-01

    Adler, Shiota and van Moerbeke observed that a tau function of the Pfaff lattice is a square root of a tau function of the Toda lattice hierarchy of Ueno and Takasaki. In this paper, we give a representation theoretical explanation for this phenomenon. We consider 2-BKP and two-component 2-KP tau functions. We shall show that a square of a BKP tau function is equal to a certain two-component KP tau function and a square of a 2-BKP tau function is equal to a certain two-component 2-KP tau function.

  12. Measurements of the tau Mass and Mass Difference of the tau^+ and tau^- at BABAR

    SciTech Connect

    Aubert, B.; Karyotakis, Y.; Lees, J.P.; Poireau, V.; Prencipe, E.; Prudent, X.; Tisserand, V.; Garra Tico, J.; Grauges, E.; Martinelli, M.; Palano, A.; Pappagallo, M.; Eigen, G.; Stugu, B.; Sun, L.; Battaglia, M.; Brown, D.N.; Kerth, L.T.; Kolomensky, Yu.G.; Lynch, G.; Osipenkov, I.L.; /UC, Berkeley /Birmingham U. /Ruhr U., Bochum /British Columbia U. /Brunel U. /Novosibirsk, IYF /UC, Irvine /UC, Riverside /UC, San Diego /UC, Santa Barbara /UC, Santa Cruz /Caltech /Cincinnati U. /Colorado U. /Colorado State U. /Dortmund U. /Dresden, Tech. U. /Ecole Polytechnique /Edinburgh U. /INFN, Ferrara /Ferrara U. /INFN, Ferrara /INFN, Ferrara /Ferrara U. /INFN, Ferrara /INFN, Ferrara /Ferrara U. /Frascati /INFN, Genoa /Genoa U. /INFN, Genoa /INFN, Genoa /Genoa U. /INFN, Genoa /INFN, Genoa /Genoa U. /Harvard U. /Heidelberg U. /Humboldt U., Berlin /Imperial Coll., London /Iowa State U. /Iowa State U. /Johns Hopkins U. /Orsay, LAL /LLNL, Livermore /Liverpool U. /Queen Mary, U. of London /Royal Holloway, U. of London /Louisville U. /Mainz U., Inst. Kernphys. /Manchester U. /Maryland U. /Massachusetts U., Amherst /MIT /McGill U. /INFN, Milan /Milan U. /INFN, Milan /INFN, Milan /Milan U. /Mississippi U. /Montreal U. /Mt. Holyoke Coll. /INFN, Naples /Naples U. /INFN, Naples /INFN, Naples /Naples U. /NIKHEF, Amsterdam /NIKHEF, Amsterdam /Notre Dame U. /Ohio State U. /Oregon U. /INFN, Padua /Padua U. /INFN, Padua /INFN, Padua /Padua U. /Paris U., VI-VII /Pennsylvania U. /INFN, Perugia /Perugia U. /INFN, Pisa /Pisa U. /INFN, Pisa /Pisa, Scuola Normale Superiore /INFN, Pisa /Pisa U. /INFN, Pisa /Princeton U. /INFN, Rome /INFN, Rome /Rome U. /INFN, Rome /INFN, Rome /Rome U. /INFN, Rome /INFN, Rome /Rome U. /INFN, Rome /INFN, Rome /Rome U. /INFN, Rome /Rostock U. /Rutherford /DAPNIA, Saclay /SLAC /South Carolina U. /Stanford U., Phys. Dept. /SUNY, Albany /Tel Aviv U. /Tennessee U. /Texas U. /Texas U., Dallas /INFN, Turin /Turin U. /INFN, Trieste /Trieste U. /Valencia U. /Victoria U. /Warwick U. /Wisconsin U., Madison

    2009-10-30

    The authors present the result of a precision measurement of the mass of the {tau} lepton, M{sub {tau}}, based on 423 fb{sup -1} of data recorded at the {Upsilon}(4S) resonance with the BABAR detector. Using a pseudomass endpoint method, they determine the mass to be 1776.68 {+-} 0.12(stat) {+-} 0.41(syst) MeV. They also measure the mass difference between the {tau}{sup +} and {tau}{sup -}, and obtain (M{sub {tau}{sup +}} - M{sub {tau}{sup -}})/M{sub AVG}{sup {tau}} = (-3.4 {+-} 1.3(stat) {+-} 0.3(syst)) x 10{sup -4}, where M{sub AVG}{sup {tau}} is the average value of M{sub {tau}{sup +}} and M{sub {tau}{sup -}}.

  13. Neuropathology of Frontotemporal Lobar Degeneration–Tau (FTLD-Tau)

    PubMed Central

    Dickson, Dennis W.; Kouri, Naomi; Murray, Melissa E.; Josephs, Keith A.

    2011-01-01

    A clinically and pathologically heterogeneous type of frontotemporal lobar degeneration has abnormal tau pathology in neurons and glia (FTLD-tau). Familial FTLD-tau is usually due to mutations in the tau gene (MAPT). Even FTLD-tau determined by MAPT mutations ha s clinical and pathologic heterogeneity. Tauopathies are subclassified according to the predominant species of tau that accumulates, with respect to alternative splicing of MAPT, with tau proteins containing 3 (3R) or 4 repeats (4R) of ~ 32 amino acids in the microtubule binding domain. In Pick's disease (PiD), 3R tau predominates, whereas 4R tau is characteristic of corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP). Depending upon the specific mutation in MAPT, familial FTLD-tau can have 3R, 4R or a combination of 3R and 4R tau. PiD is the least common FTLD-tau characterized by neuronal Pick bodies in a stereotypic neuroanatomical distribution. PSP and CBD are more common than PiD and have extensive clinical and pathologic overlap, with no distinctive clinical syndrome or biomarker that permits their differentiation. Diagnosis rests upon postmortem examination of the brain and demonstration of globose tangles, oligodendroglial coiled bodies and tufted astrocytes in PSP or threads, pretangles and astrocytic plaques in CBD. The anatomical distribution of tau pathology determines the clinical presentation of PSP and CBD, as well as PiD. The basis for this selective cortical vulnerability in FTLD-tau is unknown. PMID:21720721

  14. Tau physics results from SLD

    SciTech Connect

    Daoudi, M.; SLD Collaboration

    1996-08-10

    Results on {tau} physics at SLD are presented. They are based on 4,316 {tau}-pair events selected from a 150 k Z{sup 0} data sample collected at the SLC. These results include measurements of the {tau} lifetime ({tau}{sub r} = 288.1 {+-} 6.1 {+-} 3.3 fs), the {tau} Michel parameters ({rho} = 0.71 {+-} 0.09 {+-} 0.04, {zeta} = 1.03 {+-} 0.36 {+-} 0.05, and {zeta}{delta} = 0.84 {+-} 0.27 {+-} 0.05), and the {tau} neutrino helicity (h{sub {nu}} = {minus}0.81 {+-} 0.18 {+-} 0.03).

  15. Amyloid and tau cerebrospinal fluid biomarkers in HIV infection

    PubMed Central

    2009-01-01

    Background Because of the emerging intersections of HIV infection and Alzheimer's disease, we examined cerebrospinal fluid (CSF) biomarkers related of amyloid and tau metabolism in HIV-infected patients. Methods In this cross-sectional study we measured soluble amyloid precursor proteins alpha and beta (sAPPα and sAPPβ), amyloid beta fragment 1-42 (Aβ1-42), and total and hyperphosphorylated tau (t-tau and p-tau) in CSF of 86 HIV-infected (HIV+) subjects, including 21 with AIDS dementia complex (ADC), 25 with central nervous system (CNS) opportunistic infections and 40 without neurological symptoms and signs. We also measured these CSF biomarkers in 64 uninfected (HIV-) subjects, including 21 with Alzheimer's disease, and both younger and older controls without neurological disease. Results CSF sAPPα and sAPPβ concentrations were highly correlated and reduced in patients with ADC and opportunistic infections compared to the other groups. The opportunistic infection group but not the ADC patients had lower CSF Aβ1-42 in comparison to the other HIV+ subjects. CSF t-tau levels were high in some ADC patients, but did not differ significantly from the HIV+ neuroasymptomatic group, while CSF p-tau was not increased in any of the HIV+ groups. Together, CSF amyloid and tau markers segregated the ADC patients from both HIV+ and HIV- neuroasymptomatics and from Alzheimer's disease patients, but not from those with opportunistic infections. Conclusions Parallel reductions of CSF sAPPα and sAPPβ in ADC and CNS opportunistic infections suggest an effect of CNS immune activation or inflammation on neuronal amyloid synthesis or processing. Elevation of CSF t-tau in some ADC and CNS infection patients without concomitant increase in p-tau indicates neural injury without preferential accumulation of hyperphosphorylated tau as found in Alzheimer's disease. These biomarker changes define pathogenetic pathways to brain injury in ADC that differ from those of Alzheimer's disease

  16. The Common Core: Insights into the K-5 Standards

    ERIC Educational Resources Information Center

    McLaughlin, Maureen; Overturf, Brenda J.

    2012-01-01

    The role of the Common Core English Language Arts Standards in grades K-5 literacy instruction is the focus of the article. The authors begin by raising four questions: (1) What is the essential philosophy of the Common Core State Standards?; (2) What do educators need to know to use the College and Career Readiness Standards and Common Core State…

  17. Juneau Indian Studies Elementary Curriculum Guide. Grades K-5.

    ERIC Educational Resources Information Center

    Cadiente, Ronalda

    Designed to provide instruction in Tlingit culture as an integral part of the K-5 social studies curriculum, this guide presents teachers with extensive lesson plans and numerous resource materials. The units of study focus on the culture and environment of southeast Alaska and emphasize experiential learning activities. Each grade…

  18. Math and Economics: Implementing Authentic Instruction in Grades K-5

    ERIC Educational Resources Information Center

    Althauser, Krista; Harter, Cynthia

    2016-01-01

    The purpose of this study is to outline a partnership program that involved a local elementary school district, an institution of higher education, the local business community, and a state economic education advocacy group to integrate economics into math in grades K-5. The "Economics: Math in Real Life" program was provided in…

  19. Tau physics with polarized beams

    SciTech Connect

    Daoudi, M.

    1995-11-01

    We present the first results on tau physics using polarized beams. These include measurements of the {tau} Michel parameters {xi} and {xi}{delta} and the {tau} neutrino helicity h{sub {nu}}. The measurements were performed using the SLD detector at the Stanford Linear Collider (SLC).

  20. Review of tau lepton decays

    SciTech Connect

    Stoker, D.P.

    1991-07-01

    Measurements of the {tau} decay modes are reviewed and compared with the predictions of the Standard Model. While the agreement is generally good, the status of the 1-prong puzzle'' remains controversial and a discrepancy between the measured leptonic branching fractions and the {tau} lifetime persists. Prospects for precision measurements at a Tau-Charm Factory are also reviewed. 20 refs., 2 tabs.

  1. Measurements of the decays tau/sup -/. -->. rho/sup -/. nu. /sub tau/, tau/sup -/. -->. pi. /sup -/. nu. /sub tau/ and tau/sup -/. -->. K*-(892). nu. /sub tau/ using the MARK II detector at SPEAR

    SciTech Connect

    Dorfan, J.

    1981-04-01

    Measurements of the branching fractions for the Cabibbo favored decays tau/sup -/ ..-->.. rho/sup -/ ..-->.. ..pi../sup -/..nu../sub tau/ and the Cabibbo suppressed decay mode tau/sup -/ ..-->.. K*/sup -/ (892)..nu../sub tau/ are presented. The energy dependence of the tau/sup +/tau/sup -/ production cross section is obtained for the decays tau/sup -/ ..-->.. rho/sup -/..nu../sub tau/ and these spectra agree well with the classification of the tau/sup -/ as a spin-1/2 point particle. Fits to the production cross section yield a measurement of M/sub tau/ = (1787 +- 10) MeV/c/sup 2/ for the tau mass. Ninety-five percent confidence upper limits for the forbidden decay tau/sup -/ ..-->.. K*/sup -/(1430)..nu../sub tau/ and the tau neutrino mass are presented.

  2. Potential synergy between tau aggregation inhibitors and tau chaperone modulators

    PubMed Central

    2013-01-01

    Tau is a soluble, microtubule-associated protein known to aberrantly form amyloid-positive aggregates. This pathology is characteristic for more than 15 neuropathies, the most common of which is Alzheimer’s disease. Finding therapeutics to reverse or remove this non-native tau state is of great interest; however, at this time only one drug is entering phase III clinical trials for treating tauopathies. Generally, tau manipulation by therapeutics can either directly or indirectly alter tau aggregation and stability. Drugs that bind and change the conformation of tau itself are largely classified as aggregation inhibitors, while drugs that alter the activity of a tau-effector protein fall into several categories, such as kinase inhibitors, microtubule stabilizers, or chaperone modulators. Chaperone inhibitors that have proven effective in tau models include heat shock protein 90 inhibitors, heat shock protein 70 inhibitors and activators, as well as inducers of heat shock proteins. While many of these compounds can alter tau levels and/or aggregation states, it is possible that combining these approaches may produce the most optimal outcome. However, because many of these compounds have multiple off-target effects or poor blood–brain barrier permeability, the development of this synergistic therapeutic strategy presents significant challenges. This review will summarize many of the drugs that have been identified to alter tau biology, with special focus on therapeutics that prevent tau aggregation and regulate chaperone-mediated clearance of tau. PMID:24041111

  3. TAU2012 Summary

    NASA Astrophysics Data System (ADS)

    Pich, Antonio

    2014-08-01

    The main highlights discussed at TAU2012 are briefly summarized. Besides the standard topics on lepton physics covered also at previous conferences (universality, QCD tests, Vus determination from τ decay, g - 2, ν oscillations, lepton-flavour violation), the τ lepton is playing now a very important role in searches for new physics phenomena.

  4. Neuronal activity enhances tau propagation and tau pathology in vivo.

    PubMed

    Wu, Jessica W; Hussaini, S Abid; Bastille, Isle M; Rodriguez, Gustavo A; Mrejeru, Ana; Rilett, Kelly; Sanders, David W; Cook, Casey; Fu, Hongjun; Boonen, Rick A C M; Herman, Mathieu; Nahmani, Eden; Emrani, Sheina; Figueroa, Y Helen; Diamond, Marc I; Clelland, Catherine L; Wray, Selina; Duff, Karen E

    2016-08-01

    Tau protein can transfer between neurons transneuronally and trans-synaptically, which is thought to explain the progressive spread of tauopathy observed in the brain of patients with Alzheimer's disease. Here we show that physiological tau released from donor cells can transfer to recipient cells via the medium, suggesting that at least one mechanism by which tau can transfer is via the extracellular space. Neuronal activity has been shown to regulate tau secretion, but its effect on tau pathology is unknown. Using optogenetic and chemogenetic approaches, we found that increased neuronal activity stimulates the release of tau in vitro and enhances tau pathology in vivo. These data have implications for disease pathogenesis and therapeutic strategies for Alzheimer's disease and other tauopathies. PMID:27322420

  5. Analysis of E. coli K5 capsular polysaccharide heparosan

    PubMed Central

    Ly, Mellisa; Wang, Zhenyu; Laremore, Tatiana N.; Zhang, Fuming; Zhong, Weihong; Pu, Dennis; Zagorevski, Dmitri V.; Dordick, Jonathan S.; Linhardt, Robert J.

    2012-01-01

    Heparosan is the key precursor for the preparation of bioengineered heparin, a potential replacement for porcine intestinal heparin, an important anticoagulant drug. The molecular weight (MW) distribution of heparosan produced by the fermentation of E. coli K5 was investigated. Large-slab isocratic and mini-slab gradient polyacrylamide gel electrophoresis (PAGE) were used to analyze the MW and polydispersity of heparosan. A preparative method that allowed fractionation by continuous-elution PAGE was used to obtain heparosan MW standards. The MWs of the heparosan standards were determined by electrospray ionization Fourier-transform mass spectrometry (ESI-FT-MS). A ladder of the standards was then used to determine the MW properties of polydisperse heparosan samples. Unbleached and bleached heparosan produced by fermentation of E. coli K5 had similar number-averaged MWs (MN), weight-averaged MWs (MW), and MW ranges of 3,000 to 150,000 Da. PMID:20407891

  6. Tau Biology and Tau-Directed Therapies for Alzheimer's Disease.

    PubMed

    Bakota, Lidia; Brandt, Roland

    2016-03-01

    Alzheimer's disease (AD) is characterised by a progressive loss of cognitive functions. Histopathologically, AD is defined by the presence of extracellular amyloid plaques containing Aβ and intracellular neurofibrillary tangles composed of hyperphosphorylated tau proteins. According to the now well-accepted amyloid cascade hypothesis is the Aβ pathology the primary driving force of AD pathogenesis, which then induces changes in tau protein leading to a neurodegenerative cascade during the progression of disease. Since many earlier drug trials aiming at preventing Aβ pathology failed to demonstrate efficacy, tau and microtubules have come into focus as prominent downstream targets. The article aims to develop the current concept of the involvement of tau in the neurodegenerative triad of synaptic loss, cell death and dendritic simplification. The function of tau as a microtubule-associated protein and versatile interaction partner will then be introduced and the rationale and progress of current tau-directed therapy will be discussed in the biological context. PMID:26729186

  7. YES 2K5: Young Engineers and Scientists Mentorship Program

    NASA Astrophysics Data System (ADS)

    Boice, D. C.; Asbell, H. E.

    2005-12-01

    The Young Engineers and Scientists (YES) Program is a community partnership between Southwest Research Institute (SwRI), and local high schools in San Antonio, Texas (USA). YES has been highly successful during the past 13 years, and YES 2K5 continued this trend. It provides talented high school juniors and seniors a bridge between classroom instruction and real-world, research experiences in physical sciences (including space science and astronomy) and engineering. YES 2K5 consists of two parts: 1) an intensive three-week summer workshop held at SwRI where students experience the research environment first-hand; develop skills and acquire tools for solving scientific problems, attend mini-courses and seminars on electronics, computers and the Internet, careers, science ethics, and other topics; and select individual research projects to be completed during the academic year; and 2) a collegial mentorship where students complete individual research projects under the guidance of their mentors during the academic year and earn honors credit. At the end of the school year, students publicly present and display their work, acknowledging their accomplishments and spreading career awareness to other students and teachers. YES 2K5 developed a website for the Magnetospheric Multiscale Mission (MMS) from the perspective of a high school student. Over the past 13 years, all YES graduates have entered college, several have worked for SwRI, and three scientific publications have resulted. Student evaluations indicate the effectiveness of YES on their academic preparation and choice of college majors. We acknowledge funding from the NASA MMS Mission, the NASA E/PO program, and local charitable foundations.

  8. Gamma (K5 Based) Compressor Blade Material Design - Alpha Extrusion on a Small Scale

    NASA Technical Reports Server (NTRS)

    Kim, Young-Won

    2003-01-01

    The objective of the 2003 study is to develop a mechanically processed, high temperature TiAl alloy for use in the Turbine Based Combined Cycle compressor. An aging study with 3 temperatures and 4 time periods at each temperature will be conducted to determine the optimum aging condition. High-magnification microscopic analyses shall be employed to define the size distribution of carbide as a function of aging temperature/time. The contractor shall define optimum materials' conditions by conducting tensile and creep testing for two over-aging conditions for both alloys and fatigue testing for one over-aging condition for each alloy.

  9. Decays of the heavy lepton, tau (1785)

    SciTech Connect

    Blocker, C.A.

    1980-04-01

    The structure of the weak hadronic current coupled to the tau is investigated via some of the hadronic decays of the tau. The vector current coupling is determined by measuring the tau ..-->.. rho ..nu../sub tau/ branching ratio. The axial-vector coupling is determined by measuring the tau ..-->.. ..pi.. ..nu../sub tau/ branching ratio. The Cabibbo structure of the hadronic current is established by observing the decay tau ..-->.. K*(890)..nu../sub tau/ and measuring its branching ratio. The branching ratios for the decays tau ..-->.. e anti ..nu../sub e/..nu../sub tau/ and tau ..-->.. ..mu.. anti ..nu../sub ..mu../..nu../sub tau/ are measured as a normalization for the hadronic decays and as a check on the validity of the measurements. The leptonic branching ratios agree well with previous experiments. From a kinematic fit to the pion energy spectrum in the decay tau ..-->.. ..pi.. ..nu../sub tau/, an upper limit (95% confidence level) of 245 MeV is placed on the tau neutrino mass. From a simultaneous fit of the center of mass energy dependence of the tau production cross section and the pion energy spectrum in the decay tau ..-->.. ..pi.. ..nu../sub tau/, the tau mass is determined to be 1.787 +- .010 GeV/c. All properties of the tau measured here are consistent with it being a sequential lepton coupled to the ordinary weak hadronic current.

  10. Tau physics at future facilities

    SciTech Connect

    Perl, M.L.

    1994-12-01

    This paper dicusses and projects the tau research which may be carried out at CESR, at BEPC, at the SLC, in the next few years at LEP I, at the asymmetric B-factories under construction in Japan and the United States and, if built, a tau-charm factory. As the size of tau data sets increases, there is an increasing need to reduce the effects of systematic errors on the precision and search range of experiments. In most areas of tau physics there is a large amount of progress to be made, but in a few areas it will be difficult to substantially improve the precision of present measurements.

  11. Tau imaging in neurodegenerative diseases.

    PubMed

    Dani, M; Brooks, D J; Edison, P

    2016-06-01

    Aggregated tau protein is a major neuropathological substrate central to the pathophysiology of neurodegenerative diseases such as Alzheimer's disease (AD), frontotemporal dementia, progressive supranuclear palsy, corticobasal degeneration and chronic traumatic encephalopathy. In AD, it has been shown that the density of hyperphosphorylated tau tangles correlates closely with neuronal dysfunction and cell death, unlike β-amyloid. Until now, diagnostic and pathologic information about tau deposition has only been available from invasive techniques such as brain biopsy or autopsy. The recent development of selective in-vivo tau PET imaging ligands including [(18)F]THK523, [(18)F]THK5117, [(18)F]THK5105 and [(18)F]THK5351, [(18)F]AV1451(T807) and [(11)C]PBB3 has provided information about the role of tau in the early phases of neurodegenerative diseases, and provided support for diagnosis, prognosis, and imaging biomarkers to track disease progression. Moreover, the spatial and longitudinal relationship of tau distribution compared with β - amyloid and other pathologies in these diseases can be mapped. In this review, we discuss the role of aggregated tau in tauopathies, the challenges posed in developing selective tau ligands as biomarkers, the state of development in tau tracers, and the new clinical information that has been uncovered, as well as the opportunities for improving diagnosis and designing clinical trials in the future. PMID:26572762

  12. Effects of tau domain-specific antibodies and intravenous immunoglobulin on tau aggregation and aggregate degradation.

    PubMed

    Esteves-Villanueva, Jose O; Trzeciakiewicz, Hanna; Loeffler, David A; Martić, Sanela

    2015-01-20

    Tau pathology, including neurofibrillary tangles, develops in Alzheimer's disease (AD). The aggregation and hyperphosphorylation of tau are potential therapeutic targets for AD. Administration of anti-tau antibodies reduces tau pathology in transgenic "tauopathy" mice; however, the optimal tau epitopes and conformations to target are unclear. Also unknown is whether intravenous immunoglobulin (IVIG) products, currently being evaluated in AD trials, exert effects on pathological tau. This study examined the effects of anti-tau antibodies targeting different tau epitopes and the IVIG Gammagard on tau aggregation and preformed tau aggregates. Tau aggregation was assessed by transmission electron microscopy and fluorescence spectroscopy, and the binding affinity of the anti-tau antibodies for tau was evaluated by enzyme-linked immunosorbent assays. Antibodies used were anti-tau 1-150 ("D-8"), anti-tau 259-266 ("Paired-262"), anti-tau 341-360 ("A-10"), and anti-tau 404-441 ("Tau-46"), which bind to tau's N-terminus, microtubule binding domain (MBD) repeat sequences R1 and R4, and the C-terminus, respectively. The antibodies Paired-262 and A-10, but not D-8 and Tau-46, reduced tau fibrillization and degraded preformed tau aggregates, whereas the IVIG reduced tau aggregation but did not alter preformed aggregates. The binding affinities of the antibodies for the epitope for which they were specific did not appear to be related to their effects on tau aggregation. These results confirm that antibody binding to tau's MBD repeat sequences may inhibit tau aggregation and indicate that such antibodies may also degrade preformed tau aggregates. In the presence of anti-tau antibodies, the resulting tau morphologies were antigen-dependent. The results also suggested the possibility of different pathways regulating antibody-mediated inhibition of tau aggregation and antibody-mediated degradation of preformed tau aggregates. PMID:25545358

  13. UX Tau A

    NASA Technical Reports Server (NTRS)

    2007-01-01

    This is an artist's rendition of the one-million-year-old star system called UX Tau A, located approximately 450 light-years away. Observations from NASA's Spitzer Space Telescope showed a gap in the dusty planet-forming disk swirling around the system's central sun-like star.

    Spitzer saw a gap in UX Tau A's disk that extends from 0.2 to 56 astronomical units (an astronomical unit is the distance between the sun and Earth). The gap extends from the equivalent of Mercury to Pluto in our solar system, and is sandwiched between thick inner and outer disks on either side. Astronomers suspect that the gap was carved out by one or more forming planets.

    Such dusty disks are where planets are thought to be born. Dust grains clump together like snowballs to form larger rocks, and then the bigger rocks collide to form the cores of planets. When rocks revolve around their central star, they act like cosmic vacuum cleaners, picking up all the gas and dust in their path and creating gaps.

    Although gaps have been detected in disks swirling around young stars before, UX Tau A is special because the gap is sandwiched between two thick disks of dust. An inner thick dusty disk hugs the central star, then, moving outward, there is a gap, followed by another thick doughnut-shaped disk. Other systems with gaps contain very little to no dust near the central star. In other words, those gaps are more like big holes in the centers of disks.

    Some scientists suspect that these holes could have been carved out by a process called photoevaporation. Photoevaporation occurs when radiation from the central star heats up the gas and dust around it to the point where it evaporates away. The fact that there is thick disk swirling extremely close to UX Tau A's central star rules out the photoevaporation scenario. If photoevaporation from the star played a role, then large amounts of dust would not be floating so close to the star.

  14. Results of tests of weathered K5NA closeout material in the MSFC Hot Gas Facility

    NASA Technical Reports Server (NTRS)

    Dean, W. G.

    1982-01-01

    The application of K5NA over hypolon was investigated. The effects of using K5NA over painted cork surfaces, the effects of weathering on the unpainted K5NA surfaces are determined, and the use of water versus solvent for tooling K5NA in place were compared. It is concluded that: (1) K5NA can be applied to hypalon surfaces; (2) K5NA can be left unpainted; and (3) K5NA can be tested with water or solvent.

  15. Interactions between Tau and α-synuclein augment neurotoxicity in a Drosophila model of Parkinson's disease

    PubMed Central

    Roy, Bidisha; Jackson, George R.

    2014-01-01

    Clinical and pathological studies have suggested considerable overlap between tauopathies and synucleinopathies. Several genome-wide association studies have identified alpha-Synuclein (SNCA) and Tau (MAPT) polymorphisms as common risk factors for sporadic Parkinson's disease (PD). However, the mechanisms by which subtle variations in the expression of wild-type SNCA and MAPT influence risk for PD and the underlying cellular events that effect neurotoxicity remain unclear. To examine causes of neurotoxicity associated with the α-Syn/Tau interaction, we used the fruit fly as a model. We utilized misexpression paradigms in three different tissues to probe the α-Syn/Tau interaction: the retina, dopaminergic neurons and the larval neuromuscular junction. Misexpression of Tau and α-Syn enhanced a rough eye phenotype and loss of dopaminergic neurons in fly tauopathy and synucleinopathy models, respectively. Our findings suggest that interactions between α-Syn and Tau at the cellular level cause disruption of cytoskeletal organization, axonal transport defects and aberrant synaptic organization that contribute to neuronal dysfunction and death associated with sporadic PD. α-Syn did not alter levels of Tau phosphorylated at the AT8 epitope. However, α-Syn and Tau colocalized in ubiquitin-positive aggregates in eye imaginal discs. The presence of Tau also led to an increase in urea soluble α-Syn. Our findings have important implications in understanding the cellular and molecular mechanisms underlying α-Syn/Tau-mediated synaptic dysfunction, which likely arise in the early asymptomatic phase of sporadic PD. PMID:24430504

  16. Using Human iPSC-Derived Neurons to Model TAU Aggregation

    PubMed Central

    Verheyen, An; Diels, Annick; Dijkmans, Joyce; Oyelami, Tutu; Meneghello, Giulia; Mertens, Liesbeth; Versweyveld, Sofie; Borgers, Marianne; Buist, Arjan; Peeters, Pieter; Cik, Miroslav

    2015-01-01

    Alzheimer’s disease and frontotemporal dementia are amongst the most common forms of dementia characterized by the formation and deposition of abnormal TAU in the brain. In order to develop a translational human TAU aggregation model suitable for screening, we transduced TAU harboring the pro-aggregating P301L mutation into control hiPSC-derived neural progenitor cells followed by differentiation into cortical neurons. TAU aggregation and phosphorylation was quantified using AlphaLISA technology. Although no spontaneous aggregation was observed upon expressing TAU-P301L in neurons, seeding with preformed aggregates consisting of the TAU-microtubule binding repeat domain triggered robust TAU aggregation and hyperphosphorylation already after 2 weeks, without affecting general cell health. To validate our model, activity of two autophagy inducers was tested. Both rapamycin and trehalose significantly reduced TAU aggregation levels suggesting that iPSC-derived neurons allow for the generation of a biologically relevant human Tauopathy model, highly suitable to screen for compounds that modulate TAU aggregation. PMID:26720731

  17. Tau decays: A theoretical perspective

    SciTech Connect

    Marciano, W.J.

    1992-11-01

    Theoretical predictions for various tau decay rates are reviewed. Effects of electroweak radiative corrections are described. Implications for precision tests of the standard model and ``new physics`` searches are discussed. A perspective on the tau decay puzzle and 1-prong problem is given.

  18. Tau decays: A theoretical perspective

    SciTech Connect

    Marciano, W.J.

    1992-11-01

    Theoretical predictions for various tau decay rates are reviewed. Effects of electroweak radiative corrections are described. Implications for precision tests of the standard model and new physics'' searches are discussed. A perspective on the tau decay puzzle and 1-prong problem is given.

  19. Tau identification at the Tevatron

    SciTech Connect

    Levy, Stephen; /Chicago U., EFI

    2005-07-01

    Methods for reconstructing and identifying the hadronic decays of tau leptons with the CDF and D0 detectors at the Fermilab Tevatron collider in Run II are described. Precision electroweak measurements of W and Z gauge boson cross sections are presented as well as results of searches for physics beyond the Standard Model with hadronically decaying tau leptons in the final state.

  20. Survivability of Psychrobacter cryohalolentis K5 Under Simulated Martian Surface Conditions

    NASA Technical Reports Server (NTRS)

    Smith, David J.; Schuerger, Andrew C.; Davidson, Mark M.; Pacala, Stephen W.; Bakermans, Corien; Onstott, Tullis

    2008-01-01

    Spacecraft launched to Mars can retain viable terrestrial microorganisms on board that may survive the interplanetary transit. Such biota might compromise the search for life beyond Earth if capable of propagating on Mars. The current study explored the survivability of Psychrobacter cryohalolentis K5, a psychrotolerant microorganism obtained from a Siberian permafrost cryopeg, under simulated martian surface conditions of high ultraviolet irradiation, high desiccation, low temperature, and low atmospheric pressure. First, a desiccation experiment compared the survival of P. cryohalolentis cells embedded, or not embedded, within a medium/salt matrix (MSM) maintained at 25 degrees C for 24 hr within a laminar flow hood. Results indicate that the presence of the MSM enhanced survival of the bacterial cells by 1 to 3 orders of magnitude. Second, tests were conducted in a Mars Simulation Chamber to determine the UV tolerance of the microorganism. No viable vegetative cells of P. cryohalolentis were detected after 8 hr of exposure to Mars-normal conditions of 4.55 W/m(2) UVC irradiation (200-280 nm), -12.5 degrees C, 7.1 mbar, and a Mars gas mix composed of CO2 (95.3%), N2 (2.7%), Ar (1.6%), O2 (0.2%), and H(2)O (0.03%). Third, an experiment was conducted within the Mars chamber in which total atmospheric opacities were simulated at tau = 0.1 (dust-free CO2 atmosphere at 7.1 mbar), 0.5 (normal clear sky with 0.4 = dust opacity and 0.1 = CO2-only opacity), and 3.5 (global dust storm) to determine the survivability of P. cryohalolentis to partially shielded UVC radiation. The survivability of the bacterium increased with the level of UVC attenuation, though population levels still declined several orders of magnitude compared to UVC-absent controls over an 8 hr exposure period.

  1. The Tau-Charm Factory and tau physics

    SciTech Connect

    Perl, M.L.

    1989-04-01

    An international group of physicists is developing the concept and design of a Tau-Charm Factory: a two-ring, electron-positron, circular collider with 1.5 /< =/ /radical/s /< =/ 4.2 GeV and a design luminosity of 10/sup 33/ cm/sup /minus/2/ s/sup /minus/1/. This paper presents the concept of the facility and outlines the tau lepton physics which can be done. A companion talk by R. Schindler discusses the D/sup 0/, D/sup /+-//, and D/sub s/ physics at a Tau-Charm Factory. 25 refs., 2 tabs.

  2. Tau exon 10 alternative splicing and tauopathies

    PubMed Central

    Liu, Fei; Gong, Cheng-Xin

    2008-01-01

    Abnormalities of microtubule-associated protein tau play a central role in neurofibrillary degeneration in several neurodegenerative disorders that collectively called tauopathies. Six isoforms of tau are expressed in adult human brain, which result from alternative splicing of pre-mRNA generated from a single tau gene. Alternative splicing of tau exon 10 results in tau isoforms containing either three or four microtubule-binding repeats (3R-tau and 4R-tau, respectively). Approximately equal levels of 3R-tau and 4R-tau are expressed in normal adult human brain, but the 3R-tau/4R-tau ratio is altered in the brains in several tauopathies. Discovery of silence mutations and intronic mutations of tau gene in some individuals with frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17), which only disrupt tau exon 10 splicing but do not alter tau's primary sequence, demonstrates that dysregulation of tau exon 10 alternative splicing and consequently of 3R-tau/4R-tau balance is sufficient to cause neurodegeneration and dementia. Here, we review the gene structure, transcripts and protein isoforms of tau, followed by the regulation of exon 10 splicing that determines the expression of 3R-tau or 4R-tau. Finally, dysregulation of exon 10 splicing of tau in several tauopathies is discussed. Understanding the molecular mechanisms by which tau exon 10 splicing is regulated and how it is disrupted in tauopathies will provide new insight into the mechanisms of these tauopathies and help identify new therapeutic targets to treat these disorders. PMID:18616804

  3. a Measurement of Tau Polarization

    NASA Astrophysics Data System (ADS)

    Walsh, Arthur Michael

    At ALEPH, polarized tau pairs are produced in e^+e^- annihilations at the Z peak. The polarization depends on the tau production angle and is measured by spin analyzing tau decays in the modes tauto{rm e}nu |nu, tautomunu |nu, tautopinu, tautorhonu and tauto{rm a}_1nu . This leads to a measurement of the Z couplings to taus and electrons, {cal A} _tau and {cal A }_{rm e}, where {cal A}_{l} = 2g_sp {V}{l}g_sp{A}{l }/(g_sp{V}{l}^2 + g_sp{A}{l}^2). The values obtained using the 1992 data are { cal A}_tau = 0.129 +/- 0.016 +/- 0.010 and {cal A} _{rm e} = 0.136 +/- 0.022 +/- 0.007, where the first error is statistical and the second is systematic. Assuming electron-tau universality leads to {cal A}_{ rm e-tau} = 0.131 +/- 0.013 +/- 0.006. This result has been combined with the published ALEPH result for the 1990 and 1991 data for a measurement of the effective weak mixing angle sin ^2 theta_sp{W}{ rm eff} = 0.2334 +/- 0.0014.

  4. Mutated tau, amyloid and neuroinflammation in Alzheimer disease-A brief review.

    PubMed

    Hung, A S M; Liang, Y; Chow, Tony C H; Tang, H C; Wu, Sharon L Y; Wai, M S M; Yew, D T

    2016-05-01

    This review discussed the importance of mutated tau, amyloid and neuroinflammatory factors and microglia in Alzheimer disease. In particular tau, CD4 and TNF alpha were included in the review and the colocalizations of these factors were highlighted. It is important to realize the Alzheimer disease may result from the interactions of these factors. Some of these factors may coexist at the same region and at the same time e.g. mutated tau and amyloid in plaques. A summary scheme of etiology leading to the disease was included. PMID:26851150

  5. Aluminum interaction with human brain tau protein phosphorylation by various kinases

    SciTech Connect

    El-Sebae, A.H.; Zeid, M.M.A.; Saleh, M.A. . Environmental Chemistry and Toxicology Lab.); Abdel-Ghany, M.E.; Shalloway, D. ); Blancato, J. . Environmental Monitoring Systems Lab.)

    1993-01-01

    Phosphorylation is an indispensable process for energy and signal transduction in biological systems. AlCl[sub 3] at 10 nM to 10 uM range activated in-vitro [[gamma]-[sup 32]P] ATP phosphorylation of the brain (tau) [Tau] protein in both normal human or E. coli expressed [Tau] forms; in the presence of the kinases P34, PKP, and PKC to a maximum at 1 mM level. AlCl[sub 3] at 100 uM to 500 uM range induced non-enzymatic phosphorylation of [Tau] with [gamma]-ATP, [gamma]-GTP, and [alpha]-GTP, and [alpha]-GTP. AlCl[sub 3] activated histone phosphorylation by P34 in a similar pattern. The hyperphosphorylation of [Tau] with [gamma]-ATP, [gamma]-GTP, and [alpha]-GTP. AlCl[sub 3] activated histone phosphorylation by P34 in a similar pattern. The hyperphosphorylation of [Tau] by Al[sup 3+] was accompanied by molecular shift and mobility retardation in SDS-PAGE. This may demonstrate the mechanism of the longterm neurological effect of Al[sup 3+] in human brain leading to the formation of the neurofibrillary tangles related to Alzeheimer's disease.

  6. Hadronic Tau Decays at BaBar

    SciTech Connect

    Nugent, I.M.; /Victoria U.

    2007-10-25

    Precision measurements of the exclusive branching fraction {tau}{sup -} {yields} K{sup -}{pi}{sup 0}{nu}{sub {tau}} and {tau}{sup -} {yields} h{sup -}h{sup -}h{sup +}{nu}{sub {tau}}, where the h represent either a pion or a kaon, from the BABAR Experiment are presented. The branching fraction for {tau}{sup -} {yields} K{sup -}K{sup -}K{sup +}{nu}{sub {tau}} is the first resonant plus non-resonant measurement of this mode and the branching fraction {tau}{sup -} {yields} {phi}{pi}{sup -}{nu}{sub {tau}} is also a first measurement. In addition we present the new measurement of the branching fraction of {tau}{sup -} {yields} {phi}K{sup -}{nu}{sub {tau}}.

  7. Increased suppression of oncolytic adenovirus carrying mutant k5 on colorectal tumor

    SciTech Connect

    Fan Junkai; Xiao Tian; Gu Jinfa; Wei Na; He Lingfeng; Ding Miao; Liu Xinyuan

    2008-09-19

    Angiogenesis plays a key role in the development of a wide variety of malignant tumors. The approach of targeting antiangiogenesis has become an important field of cancer gene therapy. In this study, the antiangiogenesis protein K5 (the kringle 5 of human plasminogen) has been mutated by changing leucine71 to arginine to form mK5. Then the ZD55-mK5, which is an oncolytic adenovirus expressing mK5, was constructed. It showed stronger inhibition on proliferation of human umbilical vein endothelial cell. Moreover, in tube formation and embryonic chorioallantoic membrane assay, ZD55-mK5 exhibited more effective antiangiogenesis than ZD55-K5. In addition, ZD55-mK5 generated obvious suppression on the growth of colorectal tumor xenografts and prolonged the life span of nude mice. These results indicate that ZD55-mK5 is a potent agent for inhibiting the tumor angiogenesis and tumor growth.

  8. Closing the tau loop: the missing tau mutation.

    PubMed

    McCarthy, Allan; Lonergan, Roisin; Olszewska, Diana A; O'Dowd, Sean; Cummins, Gemma; Magennis, Brian; Fallon, Emer M; Pender, Niall; Huey, Edward D; Cosentino, Stephanie; O'Rourke, Killian; Kelly, Brendan D; O'Connell, Martin; Delon, Isabelle; Farrell, Michael; Spillantini, Maria Grazia; Rowland, Lewis P; Fahn, Stanley; Craig, Peter; Hutton, Michael; Lynch, Tim

    2015-10-01

    Frontotemporal lobar degeneration comprises a group of disorders characterized by behavioural, executive, language impairment and sometimes features of parkinsonism and motor neuron disease. In 1994 we described an Irish-American family with frontotemporal dementia linked to chromosome 17 associated with extensive tau pathology. We named this disinhibition-dementia-parkinsonism-amyotrophy complex. We subsequently identified mutations in the MAPT gene. Eleven MAPT gene splice site stem loop mutations were identified over time except for 5' splice site of exon 10. We recently identified another Irish family with autosomal dominant early amnesia and behavioural change or parkinsonism associated with the 'missing' +15 mutation at the intronic boundary of exon 10. We performed a clinical, neuropsychological and neuroimaging study on the proband and four siblings, including two affected siblings. We sequenced MAPT and performed segregation analysis. We looked for a biological effect of the tau variant by performing real-time polymerase chain reaction analysis of RNA extracted from human embryonic kidney cells transfected with exon trapping constructs. We found a c.915+15A>C exon 10/intron 10 stem loop mutation in all affected subjects but not in the unaffected. The c.915+15A>C variant caused a shift in tau splicing pattern to a predominantly exon 10+ pattern presumably resulting in predominant 4 repeat tau and little 3 repeat tau. This strongly suggests that the c.915+15A>C variant is a mutation and that it causes frontotemporal dementia linked to chromosome 17 in this pedigree by shifting tau transcription and translation to +4 repeat tau. Tau (MAPT) screening should be considered in families where amnesia or atypical parkinsonism coexists with behavioural disturbance early in the disease process. We describe the final missing stem loop tau mutation predicted 15 years ago. Mutations have now been identified at all predicted sites within the 'stem' when the stem

  9. Identification of disulfide cross-linked tau dimer responsible for tau propagation

    PubMed Central

    Kim, Dohee; Lim, Sungsu; Haque, Md. Mamunul; Ryoo, Nayeon; Hong, Hyun Seok; Rhim, Hyewhon; Lee, Dong-Eun; Chang, Young-Tae; Lee, Jun-Seok; Cheong, Eunji; Kim, Dong Jin; Kim, Yun Kyung

    2015-01-01

    Recent evidence suggests that tau aggregates are not only neurotoxic, but also propagate in neurons acting as a seed for native tau aggregation. Prion-like tau transmission is now considered as an important pathogenic mechanism driving the progression of tau pathology in the brain. However, prion-like tau species have not been clearly characterized. To identify infectious tau conformers, here we prepared diverse tau aggregates and evaluated the effect on inducing intracellular tau-aggregation. Among tested, tau dimer containing P301L-mutation is identified as the most infectious form to induce tau pathology. Biochemical analysis reveals that P301L-tau dimer is covalently cross-linked with a disulfide bond. The relatively small and covalently cross-linked tau dimer induced tau pathology efficiently in primary neurons and also in tau-transgenic mice. So far, the importance of tau disulfide cross-linking has been overlooked in the study of tau pathology. Here our results suggested that tau disulfide cross-linking might play critical role in tau propagation by producing structurally stable and small tau conformers. PMID:26470054

  10. Identification of disulfide cross-linked tau dimer responsible for tau propagation.

    PubMed

    Kim, Dohee; Lim, Sungsu; Haque, Md Mamunul; Ryoo, Nayeon; Hong, Hyun Seok; Rhim, Hyewhon; Lee, Dong-Eun; Chang, Young-Tae; Lee, Jun-Seok; Cheong, Eunji; Kim, Dong Jin; Kim, Yun Kyung

    2015-01-01

    Recent evidence suggests that tau aggregates are not only neurotoxic, but also propagate in neurons acting as a seed for native tau aggregation. Prion-like tau transmission is now considered as an important pathogenic mechanism driving the progression of tau pathology in the brain. However, prion-like tau species have not been clearly characterized. To identify infectious tau conformers, here we prepared diverse tau aggregates and evaluated the effect on inducing intracellular tau-aggregation. Among tested, tau dimer containing P301L-mutation is identified as the most infectious form to induce tau pathology. Biochemical analysis reveals that P301L-tau dimer is covalently cross-linked with a disulfide bond. The relatively small and covalently cross-linked tau dimer induced tau pathology efficiently in primary neurons and also in tau-transgenic mice. So far, the importance of tau disulfide cross-linking has been overlooked in the study of tau pathology. Here our results suggested that tau disulfide cross-linking might play critical role in tau propagation by producing structurally stable and small tau conformers. PMID:26470054

  11. 26 CFR 1.401(k)-5 - Special rules for mergers, acquisitions and similar events. [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 5 2010-04-01 2010-04-01 false Special rules for mergers, acquisitions and similar events. 1.401(k)-5 Section 1.401(k)-5 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE.... § 1.401(k)-5 Special rules for mergers, acquisitions and similar events....

  12. 26 CFR 1.401(k)-5 - Special rules for mergers, acquisitions and similar events. [Reserved

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 5 2014-04-01 2014-04-01 false Special rules for mergers, acquisitions and similar events. 1.401(k)-5 Section 1.401(k)-5 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... Plans, Etc. § 1.401(k)-5 Special rules for mergers, acquisitions and similar events....

  13. 26 CFR 1.401(k)-5 - Special rules for mergers, acquisitions and similar events. [Reserved

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 5 2012-04-01 2011-04-01 true Special rules for mergers, acquisitions and similar events. 1.401(k)-5 Section 1.401(k)-5 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... Plans, Etc. § 1.401(k)-5 Special rules for mergers, acquisitions and similar events....

  14. 26 CFR 1.401(k)-5 - Special rules for mergers, acquisitions and similar events. [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 5 2011-04-01 2011-04-01 false Special rules for mergers, acquisitions and similar events. 1.401(k)-5 Section 1.401(k)-5 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... Plans, Etc. § 1.401(k)-5 Special rules for mergers, acquisitions and similar events....

  15. 26 CFR 1.401(k)-5 - Special rules for mergers, acquisitions and similar events. [Reserved

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 5 2013-04-01 2013-04-01 false Special rules for mergers, acquisitions and similar events. 1.401(k)-5 Section 1.401(k)-5 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... Plans, Etc. § 1.401(k)-5 Special rules for mergers, acquisitions and similar events....

  16. Accelerated Human Mutant Tau Aggregation by Knocking Out Murine Tau in a Transgenic Mouse Model

    PubMed Central

    Ando, Kunie; Leroy, Karelle; Héraud, Céline; Yilmaz, Zehra; Authelet, Michèle; Suain, Valèrie; De Decker, Robert; Brion, Jean-Pierre

    2011-01-01

    Many models of human tauopathies have been generated in mice by expression of a human mutant tau with maintained expression of mouse endogenous tau. Because murine tau might interfere with the toxic effects of human mutant tau, we generated a model in which a pathogenic human tau protein is expressed in the absence of wild-type tau protein, with the aim of facilitating the study of the pathogenic role of the mutant tau and to reproduce more faithfully a human tauopathy. The Tg30 line is a tau transgenic mouse model overexpressing human 1N4R double-mutant tau (P301S and G272V) that develops Alzheimer's disease-like neurofibrillary tangles in an age-dependent manner. By crossing Tg30 mice with mice invalidated for their endogenous tau gene, we obtained Tg30xtau−/− mice that express only exogenous human double-mutant 1N4R tau. Although Tg30xtau−/− mice express less tau protein compared with Tg30, they exhibit signs of decreased survival, increased proportion of sarkosyl-insoluble tau in the brain and in the spinal cord, increased number of Gallyas-positive neurofibrillary tangles in the hippocampus, increased number of inclusions in the spinal cord, and a more severe motor phenotype. Deletion of murine tau accelerated tau aggregation during aging of this mutant tau transgenic model, suggesting that murine tau could interfere with the development of tau pathology in transgenic models of human tauopathies. PMID:21281813

  17. Glial Tau Pathology in Tauopathies: Functional Consequences

    PubMed Central

    Kahlson, Martha A.; Colodner, Kenneth J.

    2015-01-01

    Tauopathies are a class of neurodegenerative diseases characterized by the presence of hyperphosphorylated and aggregated tau pathology in neuronal and glial cells. Though the ratio of neuronal and glial tau aggregates varies across diseases, glial tau aggregates can populate the same degenerating brain regions as neuronal tau aggregates. While much is known about the deleterious consequences of tau pathology in neurons, the relative contribution of glial tau pathology to these diseases is less clear. Recent studies using a number of model systems implicate glial tau pathology in contributing to tauopathy pathogenesis. This review aims to highlight the functional consequences of tau overexpression in glial cells and explore the potential contribution of glial tau pathology in the pathogenesis of neurodegenerative tauopathies. PMID:26884683

  18. Insulin dysfunction and Tau pathology

    PubMed Central

    El Khoury, Noura B.; Gratuze, Maud; Papon, Marie-Amélie; Bretteville, Alexis; Planel, Emmanuel

    2013-01-01

    The neuropathological hallmarks of Alzheimer's disease (AD) include senile plaques of β-amyloid (Aβ) peptides (a cleavage product of the Amyloid Precursor Protein, or APP) and neurofibrillary tangles (NFT) of hyperphosphorylated Tau protein assembled in paired helical filaments (PHF). NFT pathology is important since it correlates with the degree of cognitive impairment in AD. Only a small proportion of AD is due to genetic variants, whereas the large majority of cases (~99%) is late onset and sporadic in origin. The cause of sporadic AD is likely to be multifactorial, with external factors interacting with biological or genetic susceptibilities to accelerate the manifestation of the disease. Insulin dysfunction, manifested by diabetes mellitus (DM) might be such factor, as there is extensive data from epidemiological studies suggesting that DM is associated with an increased relative risk for AD. Type 1 diabetes (T1DM) and type 2 diabetes (T2DM) are known to affect multiple cognitive functions in patients. In this context, understanding the effects of diabetes on Tau pathogenesis is important since Tau pathology show a strong relationship to dementia in AD, and to memory loss in normal aging and mild cognitive impairment. Here, we reviewed preclinical studies that link insulin dysfunction to Tau protein pathogenesis, one of the major pathological hallmarks of AD. We found more than 30 studies reporting Tau phosphorylation in a mouse or rat model of insulin dysfunction. We also payed attention to potential sources of artifacts, such as hypothermia and anesthesia, that were demonstrated to results in Tau hyperphosphorylation and could major confounding experimental factors. We found that very few studies reported the temperature of the animals, and only a handful did not use anesthesia. Overall, most published studies showed that insulin dysfunction can promote Tau hyperphosphorylation and pathology, both directly and indirectly, through hypothermia. PMID:24574966

  19. The non-anticoagulant heparin-like K5 polysaccharide derivative K5-N,OSepi attenuates myocardial ischaemia/reperfusion injury

    PubMed Central

    Collino, Massimo; Pini, Alessandro; Mastroianni, Rosanna; Benetti, Elisa; Lanzi, Cecilia; Bani, Daniele; Chini, Jacopo; Manoni, Marco; Fantozzi, Roberto; Masini, Emanuela

    2012-01-01

    Heparin and low molecular weight heparins have been demonstrated to reduce myocardial ischaemia/reperfusion (I/R) injury, although their use is hampered by the risk of haemorrhagic and thrombotic complications. Chemical and enzymatic modifications of K5 polysaccharide have shown the possibility of producing heparin-like compounds with low anticoagulant activity and strong anti-inflammatory effects. Using a rat model of regional myocardial I/R, we investigated the effects of an epimerized N-,O-sulphated K5 polysaccharide derivative, K5-N,OSepi, on infarct size and histological signs of myocardial injury caused by 30 min. ligature of the left anterior descending coronary artery followed by 1 or 24 h reperfusion. K5-N,OSepi (0.1–1 mg/kg given i.v. 15 min. before reperfusion) significantly reduced the extent of myocardial damage in a dose-dependent manner. Furthermore, we investigated the potential mechanism(s) of the cardioprotective effect(s) afforded by K5-N,OSepi. In left ventricular samples, I/R induced mast cell degranulation and a robust increase in lipid peroxidation, free radical-induced DNA damage and calcium overload. Markers of neutrophil infiltration and activation were also induced by I/R in rat hearts, specifically myeloperoxidase activity, intercellular-adhesion-molecule-1 expression, prostaglandin-E2 and tumour-necrosis-factor-α production. The robust increase in oxidative stress and inflammatory markers was blunted by K5-N,OSepi, in a dose-dependent manner, with maximum at 1 mg/kg. Furthermore, K5-N,OSepi administration attenuated the increase in caspase 3 activity, Bid and Bax activation and ameliorated the decrease in expression of Bcl-2 within the ischaemic myocardium. In conclusion, we demonstrate that the cardioprotective effect of the non-anticoagulant K5 derivative K5-N,OSepi is secondary to a combination of anti-apoptotic and anti-inflammatory effects. PMID:22248092

  20. Reconstruction and selection of Z{yields}{tau}{tau}{yields}{mu}+{tau}-jet+{nu}'s decays at the CMS experiment

    SciTech Connect

    Lusito, Letizia

    2010-12-22

    At the LHC, tau leptons are expected in final states of many important physics processes including Supersymmetry and the production of Higgs boson(s) and other exotic particles. An efficient and accurate {tau} reconstruction and identification are therefore an important part of the CMS physics programme. Z{sup 0}{yields}{tau}{sup +}{tau}{sup -} decays are often considered the ''standard candle'' of tau reconstruction as they validate tau lepton identification and provide a test bench for Higgs searches (for which they constitute the main irreducible background). We describe techniques for selecting and reconstructing the Z{sup 0}{yields}{tau}{sup {+-}}{tau}{sup {-+}}{yields}{mu}{sup {+-}}{nu}{sub {mu}}{bar {nu}}{sub {tau}}({bar {nu}}{sub {mu}}{nu}{sub {tau}})+{tau}-jet{sup {-+}}{nu}{sub {tau}}({bar {nu}}{sub {tau}}) events that were developed for the measurement of the Z production cross-section by the CMS experiment using 200 pb{sup -1} of the LHC collision data at the center-of-mass energy {radical}(s) 10 TeV. We validate these techniques using simulated events and present a data-driven method for estimating background contributions to this measurement.

  1. From tangles to tau protein.

    PubMed

    Iqbal, K; Novak, M

    2006-01-01

    Alois Alzheimer couldn't have chosen a name more appropriate than neurofibrillary tangles when one hundred years ago (Alzheimer, 1906) he presented this histopathological hallmark of the progressive dementing disorder, which got named after him as Alzheimer disease. Both, the structure and as well as the molecular composition of neurofibrillary tangles have baffled neuroscientists for many years. It was not till 1963 when with the help of the electron microscope the tangles were found to be made up of paired helical filaments (PHF). It took another 23 years before microtubule associated protein tau was immunohistochemically identified as the part of neurofibrillary tangles (Grundke-lqbal, 1986 a). The same year it was shown that tau protein in Alzheimer disease brain was abnormally hyperphosphorylated (Grundke-Iqbal, 1986 b). In 1988 Michal Novak, Cesar Milstein and Claude Wischik produced monoclonal antibody that was able to recognize then unknown protein in PHF. The antibody (MN423) allowed its isolation and let to full molecular characterization as protein tau. These studies provided molecular proof that tau protein was the major and an integral component of the PHF (Wischik et al, 1988 a, b, Goedert et al, 1988, Novak et al, 1989, 1991). Over the years the significance of tau pathology for the neurodegenerative diseases was discussed and often questioned. However, detailed studies of the maturation and distribution of NFTs, showing correlation with degree of cognitive decline and memory impairment in Alzheimer's disease (Braak and Braak, 1991), together with discovery of tau gene mutations causing fronto-temporal dementia in many families (Hutton et al, 1998) promoted tau as the major pathogenic force in neurodegenerative cascade. Further studies focused on tau dysfunctions revealed truncation and phosphorylation as two major posttranslational modifications responsible for toxic gain of function as an underlying cause of tauopathies including Alzheimer

  2. Tau decays into K* mesons

    NASA Astrophysics Data System (ADS)

    Albrecht, H.; Hamacher, T.; Hofmann, R. P.; Kirchhoff, T.; Mankel, R.; Nau, A.; Nowak, S.; Schröder, H.; Schulz, H. D.; Walter, M.; Wurth, R.; Hast, C.; Kapitza, H.; Kolanoski, H.; Kosche, A.; Lange, A.; Lindner, A.; Schieber, M.; Siegmund, T.; Spaan, B.; Thurn, H.; Töpfer, D.; Wegener, D.; Eckstein, P.; Schubert, K. R.; Schwierz, R.; Waldi, R.; Reim, K.; Wegener, H.; Eckmann, R.; Kuipers, H.; Mai, O.; Mundt, R.; Oest, T.; Reiner, R.; Schmidt-Parzefall, W.; Stiewe, J.; Werner, S.; Ehret, K.; Hofmann, W.; Hüpper, A.; Knöpfle, K. T.; Spengler, J.; Krieger, P.; Macfarlane, D. B.; Saull, P. R. B.; Tzamariudaki, K.; van de Water, R. G.; Yoon, T.-S.; Frankl, C.; Reßing, D.; Schmidtler, M.; Schneider, M.; Weseler, S.; Kernel, G.; Križan, P.; Križnič, E.; Podobnik, T.; Živko, T.; Balagura, V.; Belyaev, I.; Schechelnitsky, S.; Danilov, M.; Doutskoy, A.; Gershtein, Yu.; Golutvin, A.; Korolko, I.; Kostina, G.; Litvintsev, D.; Lubimov, V.; Pakhlov, P.; Semenov, S.; Snizhko, A.; Tichomirov, I.; Zaitsev, Yu.

    1995-06-01

    Using the ARGUS detector at the storage ring DORIS II we have measured τ decays into three charged mesons containing K * mesons. Exploiting the good particle identification capabilities of the detector we have determined the following branching ratios:Brleft( {tau ^ - to overline {K^{*0} } π ^ - v_tau } right) = left( {0.25 ± 0.10 ± 0.05} right)% , B r (τ-→ K *0 K - v τ)= (0.20±0.05±0.04)%, and B r (τ-→ K *- X 0 v τ) =(1.15±0.15-0.18 +0.13)%.

  3. The. tau. -lepton and its associated neutrino

    SciTech Connect

    Pich, A. )

    1990-10-10

    This paper discusses the {tau}-lepton and the prospects for future improvements. It is shown how a better understanding of the {tau} properties could be used for testing fundamental aspects of the electroweak and strong interactions.

  4. Tau Splicing and the Intricacies of Dementia

    PubMed Central

    Andreadis, Athena

    2011-01-01

    Tau is a microtubule associated protein that fulfills several functions critical for neuronal formation and health. Tau discharges its functions by producing multiple isoforms via regulated alternative splicing. These isoforms modulate tau function in normal brain by altering the domains of the protein, thereby influencing its localization, conformation and post-translational modifications and hence its availability and affinity for microtubules and other ligands. Disturbances in tau expression result in disruption of the neuronal cytoskeleton and formation of tau structures (neurofibrillary tangles) found in brains of dementia sufferers. More specifically, aberrations in tau splicing regulation directly cause several neurodegenerative diseases which lead to dementia. In this review, I present our cumulative knowledge of tau splicing regulation in connection with neurodegeneration and also briefly go over the still-extensive list of questions that are connected to tau (dys)function. PMID:21604267

  5. Interaction of tau with the RNA-Binding Protein TIA1 Regulates tau Pathophysiology and Toxicity.

    PubMed

    Vanderweyde, Tara; Apicco, Daniel J; Youmans-Kidder, Katherine; Ash, Peter E A; Cook, Casey; Lummertz da Rocha, Edroaldo; Jansen-West, Karen; Frame, Alissa A; Citro, Allison; Leszyk, John D; Ivanov, Pavel; Abisambra, Jose F; Steffen, Martin; Li, Hu; Petrucelli, Leonard; Wolozin, Benjamin

    2016-05-17

    Dendritic mislocalization of microtubule associated protein tau is a hallmark of tauopathies, but the role of dendritic tau is unknown. We now report that tau interacts with the RNA-binding protein (RBP) TIA1 in brain tissue, and we present the brain-protein interactome network for TIA1. Analysis of the TIA1 interactome in brain tissue from wild-type (WT) and tau knockout mice demonstrates that tau is required for normal interactions of TIA1 with proteins linked to RNA metabolism, including ribosomal proteins and RBPs. Expression studies show that tau regulates the distribution of TIA1, and tau accelerates stress granule (SG) formation. Conversely, TIA1 knockdown or knockout inhibits tau misfolding and associated toxicity in cultured hippocampal neurons, while overexpressing TIA1 induces tau misfolding and stimulates neurodegeneration. Pharmacological interventions that prevent SG formation also inhibit tau pathophysiology. These studies suggest that the pathophysiology of tauopathy requires an intimate interaction with RNA-binding proteins. PMID:27160897

  6. Tau Trigger at the ATLAS Experiment

    SciTech Connect

    Benslama, K.; Kalinowski, A.; Belanger-Champange, C.; Brenner, R.; Bosman, M.; Casado, P.; Osuna, C.; Perez, E.; Vorwerk, V.; Czyczula, Z.; Dam, M.; Xella, S.; Demers, S.; Farrington, S.; Igonkina, O.; Kanaya, N.; Tsuno, S.; Ptacek, E.; Reinsch, A.; Strom, David M.; Torrence, E.; /Oregon U. /Sydney U. /Lancaster U. /Birmingham U.

    2011-11-09

    Many theoretical models, like the Standard Model or SUSY at large tan({beta}), predict Higgs bosons or new particles which decay more abundantly to final states including tau leptons than to other leptons. At the energy scale of the LHC, the identification of tau leptons, in particular in the hadronic decay mode, will be a challenging task due to an overwhelming QCD background which gives rise to jets of particles that can be hard to distinguish from hadronic tau decays. Equipped with excellent tracking and calorimetry, the ATLAS experiment has developed tau identification tools capable of working at the trigger level. This contribution presents tau trigger algorithms which exploit the main features of hadronic tau decays and describes the current tau trigger commissioning activities. Many of the SM processes being investigated at ATLAS, as well as numerous BSM searches, contain tau leptons in their final states. Being able to trigger effectively on the tau leptons in these events will contribute to the success of the ATLAS experiment. The tau trigger algorithms and monitoring infrastructure are ready for the first data, and are being tested with the data collected with cosmic muons. The development of efficiency measurements methods using QCD and Z {yields} {tau}{tau} events is well advanced.

  7. Tau Decays at BaBar

    SciTech Connect

    Hast, Carsten; /SLAC

    2009-01-22

    Recent results of tau lepton decay studies based on luminosities between 350 fb{sup -1} and 469 fb{sup -1} collected with the BABAR detector at the PEP-II e{sup +}e{sup -} collider at the SLAC National Accelerator Laboratory are presented. The analyses reported here are Charged Current Lepton Universality and measurements of |V{sub us}| using {tau}{sup -} {yields} e{sup -}{bar {nu}}{sub e}{nu}{sub {tau}}, {mu}{sup -}{bar {nu}}{sub {mu}}{nu}{sub {tau}}, {pi}{sup -} {nu}{sub {tau}}, and K{sup -}{nu}{sub {tau}} decays, as well as searches for Second Class Currents in {tau}{sup -} {yields} {omega}{pi}{sup -}{nu}{sub {tau}} decays, studies of Lepton Flavor Violations, and a tau mass measurement and CPT-Test. If not explicitly mentioned, charge conjugate decay modes are also implied. decays, as well as searches for Second Class Currents in {tau}{sup -} {yields} {omega}{pi}{sup -}{nu}{sub {tau}} decays, studies of Lepton Flavor Violations, and a tau mass measurement and CPT-Test. If not explicitly mentioned, charge conjugate decay modes are also implied.

  8. A Tau-Charm Factory at CEBAF

    SciTech Connect

    Seth, K.K.

    1994-04-01

    It is proposed that a Tau Charm Factory represents a natural extension of CEBAF into higher energy domains. The exciting nature of the physics of charm quarks and tau leptons is briefly reviewed and it is suggested that the concept of a linac-ring collider as a Tau Charm Factory at CEBAF should be seriously studied.

  9. Prospect for measuring the CP phase in the $h\\tau\\tau$ coupling at the LHC

    SciTech Connect

    Askew, Andrew; Jaiswal, Prerit; Okui, Takemichi; Prosper, Harrison B.; Sato, Nobuo

    2015-04-01

    The search for a new source of CP violation is one of the most important endeavors in particle physics. A particularly interesting way to perform this search is to probe the CP phase in the $h\\tau\\tau$ coupling, as the phase is currently completely unconstrained by all existing data. Recently, a novel variable $\\Theta$ was proposed for measuring the CP phase in the $h\\tau\\tau$ coupling through the $\\tau^\\pm \\to \\pi^\\pm \\pi^0 \

  10. Tau identification at D0

    SciTech Connect

    Galea, Cristina; /Radboud U. Nijmegen

    2006-12-01

    We describe methods to identify {tau} leptons produced in high energy p{bar p} collisions ({radical}s = 1.96 GeV) at the Tevatron, using the D0 detector. Different procedures used for discrimination against background particles misidentified as taus are also discussed. Finally, we present some physics results obtained by applying these methods to illustrate their performance.

  11. Evidence for B+ --> tau+ nu_tau Decays using Hadronic B Tags

    SciTech Connect

    del Amo Sanchez, P.; Lees, J.P.; Poireau, V.; Prencipe, E.; Tisserand, V.; Garra Tico, J.; Grauges, E.; Martinelli, M.; Milanes, D.A.; Palano, A.; Pappagallo, M.; Eigen, G.; Stugu, B.; Sun, L.; Brown, D.N.; Kerth, L.T.; Kolomensky, Yu.G.; Lynch, G.; Osipenkov, I.L.; Koch, H.; Schroeder, T.; /Ruhr U., Bochum /British Columbia U. /Brunel U. /Novosibirsk, IYF /UC, Irvine /UC, Riverside /UC, Santa Barbara /UC, Santa Cruz /Caltech /Cincinnati U. /Colorado U. /Colorado State U. /Dortmund U. /Dresden, Tech. U. /Ecole Polytechnique /Edinburgh U. /INFN, Ferrara /Ferrara U. /INFN, Ferrara /INFN, Ferrara /Ferrara U. /INFN, Ferrara /Frascati /INFN, Genoa /Genoa U. /INFN, Genoa /INFN, Genoa /Genoa U. /INFN, Genoa /INFN, Genoa /Genoa U. /Indian Inst. Tech., Guwahati /Harvard U. /Heidelberg U. /Humboldt U., Berlin /Imperial Coll., London /Iowa State U. /Iowa State U. /Johns Hopkins U. /Orsay, LAL /LLNL, Livermore /Liverpool U. /Queen Mary, U. of London /Royal Holloway, U. of London /Louisville U. /Mainz U., Inst. Kernphys. /Manchester U. /Maryland U. /Massachusetts U., Amherst /MIT /McGill U. /INFN, Milan /Milan U. /INFN, Milan /INFN, Milan /Milan U. /Mississippi U. /Montreal U. /INFN, Naples /Naples U. /NIKHEF, Amsterdam /Notre Dame U. /Ohio State U. /Oregon U. /INFN, Padua /Padua U. /INFN, Padua /INFN, Padua /Padua U. /Paris U., VI-VII /INFN, Perugia /Perugia U. /INFN, Pisa /Pisa U. /INFN, Pisa /Pisa, Scuola Normale Superiore /INFN, Pisa /Pisa U. /INFN, Pisa /Princeton U. /INFN, Rome /INFN, Rome /Rome U. /INFN, Rome /INFN, Rome /Rome U. /INFN, Rome /INFN, Rome /Rome U. /INFN, Rome /INFN, Rome /Rome U. /Rostock U. /Rutherford /DAPNIA, Saclay /SLAC /South Carolina U. /Southern Methodist U. /Stanford U., Phys. Dept. /SUNY, Albany /Tel Aviv U. /Tennessee U. /Texas U. /Texas U., Dallas /INFN, Turin /Turin U. /INFN, Trieste /Trieste U. /Valencia U. /Victoria U. /Warwick U. /Wisconsin U., Madison

    2011-08-11

    We present a search for the decay B{sup +} --> {tau}{sup +} {nu}{sub {tau}} using 467.8 x 10{sup 6} B{anti B} pairs collected at the {Upsilon}(4S) resonance with the BABAR detector at the SLAC PEP-II B-Factory. We select a sample of events with on completely reconstructed B{sup -} in an hadronic decay mode (B{sup -} --> D{sup (*)0}X{sup -} and B{sup -} --> J/{psi} X{sup -}). We examine the rest of the event to search for a B{sup +} --> {tau}{sup +} {nu}{sub {tau}} decay. We identify the {tau}{sup +} lepton in the following modes: {tau}{sup +} --> e{sup +} {nu}{sub e}{anti {nu}}{sub {tau}}, {tau}{sup +} --> {mu}{sup +} {nu}{sub {mu}}{anti {nu}}{sub {tau}}, {tau}{sup +} --> {pi}{sup +}{anti {nu}}{sub {tau}} and {tau}{sup +} --> {rho}{anti {nu}}{sub {tau}}. We find an excess of events with respect to expected background, which excludes the null signal hypothesis at the level of 3.3 {sigma} and can be converted to a branching fraction central value of B(B{sup +} --> {tau}{sup +} {nu}{sub {tau}})= (1.80{sup + 0.57}{sub - 0.54}(stat.) {+-} 0.26 (syst.)) x 10{sup -4}.

  12. New results on the tau lepton

    SciTech Connect

    Gan, K.K.

    1987-11-01

    This is a review of new results on the tau lepton. The results include precise measurements of the lifetime, measurements of the decay tau/sup -/ ..-->.. ..pi../sup -/2..pi../sup 0/nu/sub tau/ with much improved precision, and limits on decay modes containing eta mesons, including the second-class-current decay tau/sup -/ ..-->.. ..pi../sup -/eta nu/sub tau/. The implications of these new results on the discrepancy in the one-charged-particle decay modes are discussed. 52 refs., 6 figs., 2 tabs.

  13. Measurement of the {tau} lifetime at SLD

    SciTech Connect

    Abe, K.; Abt, I.; Ahn, C.J.; Akagi, T.; Allen, N.J.; Ash, W.W.; Aston, D.; Baird, K.G.; Baltay, C.; Band, H.R.; Barakat, M.B.; Baranko, G.; Bardon, O.; Barklow, T.; Bazarko, A.O.; Ben-David, R.; Benvenuti, A.C.; Bienz, T.; Bilei, G.M.; Bisello, D.; Blaylock, G.; Bogart, J.R.; Bolton, T.; Bower, G.R.; Brau, J.E.; Breidenbach, M.; Bugg, W.M.; Burke, D.; Burnett, T.H.; Burrows, P.N.; Busza, W.; Calcaterra, A.; Caldwell, D.O.; Calloway, D.; Camanzi, B.; Carpinelli, M.; Cassell, R.; Castaldi, R.; Castro, A.; Cavalli-Sforza, M.; Church, E.; Cohn, H.O.; Coller, J.A.; Cook, V.; Cotton, R.; Cowan, R.F.; Coyne, D.G.; D`Oliveira, A.; Damerell, C.J.S.; Daoudi, M.; De Sangro, R.; De Simone, P.; Dell`Orso, R.; Dima, M.; Du, P.Y.C.; Dubois, R.; Eisenstein, B.I.; Elia, R.; Etzion, E.; Falciai, D.; Fero, M.J.; Frey, R.; Furuno, K.; Gillman, T.; Gladding, G.; Gonzalez, S.; Hallewell, G.D.; Hart, E.L.; Hasegawa, Y.; Hedges, S.; Hertzbach, S.S.; Hildreth, M.D.; Huber, J.; Huffer, M.E.; Hughes, E.W.; Hwang, H.; Iwasaki, Y.; Jackson, D.J.; Jacques, P.; Jaros, J.; Johnson, A.S.; Johnson, J.R.; Johnson, R.A.; Junk, T.; Kajikawa, R.; Kalelkar, M.; Kang, H.J.; Karliner, I.; Kawahara, H.; Kendall, H.W.; Kim, Y.; King, M.E.; King, R.; Kofler, R.R.; Krishna, N.M.; Kroeger, R.S.; Labs, J.F.; Langston, M.; Lath, A.; Lauber, J.A.; Leith, D.W.G.; Liu, M.X.; Liu, X.; Loreti, M.; Lu, A.; Lynch, H.L.; Ma, J.; Mancinelli, G.; Manly, S.; Mantovani, G.; Markiewicz, T.W.; Maruyama, T.; Massetti, R.; Masuda, H.; Mazzucato, E.; McKemey, A.K.; Meadows, B.T.; Messner, R.; Mockett, P.M.; Moffeit, K.C.; Mours, B.; Mueller, G.; Muller, D.; Nagamine, T.; Nauenberg, U.; Neal, H.; Nussbaum, M.; Ohnishi, Y.; Osborne, L.S.; Panvini, R.S.; Park, H.; Pavel, T.J.; Peruzzi, I.; Piccolo, M.; Piemontese, L.; Pieroni, E.; Pitts, K.T.; Plano, R.J.; Prepost, R.; Prescott, C.Y.; Punkar, G.D.; Quigley, J.; Ratcliff, B.N.; Reeves, T.W.; Reidy, J.; Rensing, P.E.; Rochester, L.S.; Rothberg, J.E.; Rowson, P.C.; (The SLD Collabor...

    1995-11-01

    A measurement of the lifetime of the {tau} lepton has been made using a sample of 1671 {ital Z}{sup 0}{r_arrow}{tau}{sup +}{tau}{sup {minus}} decays collected by the SLD detector at the SLC. The measurement benefits from the small and stable collision region at the SLC and the precision pixel vertex detector of the SLD. Three analysis techniques have been used: decay length, impact parameter, and impact parameter difference methods. The combined result is {tau}{sub {tau}}=297{plus_minus}9 (stat){plus_minus}5(syst) fs.

  14. A Simple Model to Study Tau Pathology

    PubMed Central

    Houck, Alexander L.; Hernández, Félix; Ávila, Jesús

    2016-01-01

    Tau proteins play a role in the stabilization of microtubules, but in pathological conditions, tauopathies, tau is modified by phosphorylation and can aggregate into aberrant aggregates. These aggregates could be toxic to cells, and different cell models have been used to test for compounds that might prevent these tau modifications. Here, we have used a cell model involving the overexpression of human tau in human embryonic kidney 293 cells. In human embryonic kidney 293 cells expressing tau in a stable manner, we have been able to replicate the phosphorylation of intracellular tau. This intracellular tau increases its own level of phosphorylation and aggregates, likely due to the regulatory effect of some growth factors on specific tau kinases such as GSK3. In these conditions, a change in secreted tau was observed. Reversal of phosphorylation and aggregation of tau was found by the use of lithium, a GSK3 inhibitor. Thus, we propose this as a simple cell model to study tau pathology in nonneuronal cells due to their viability and ease to work with. PMID:26949341

  15. Teachers' Use of and Attitudes toward Informational Text in K-5 Classrooms

    ERIC Educational Resources Information Center

    Ness, Molly

    2011-01-01

    The purposes of this research were (a) to understand the frequency with which K-5 teachers use informational text in their routine classroom instruction, (b) to understand the percentage of informational text in classroom libraries, and (c) to explore teachers' attitudes about informational text. Survey data of 318 participants indicated that K-5

  16. Characterization of a Unique Undergraduate Multidisciplinary STEM K-5 Teacher Preparation Program

    ERIC Educational Resources Information Center

    O'Brien, Steve

    2010-01-01

    The K-5 school years are crucial, setting the framework for all subjects as well as critical thinking skills. The single most important component in a classroom is the teacher. However, in a formative timeframe for elementary-school aged children, the number of K-5 teachers that are educated with a Science, Technology, Engineering or Math…

  17. Extracellular Monomeric Tau Protein Is Sufficient to Initiate the Spread of Tau Protein Pathology*

    PubMed Central

    Michel, Claire H.; Kumar, Satish; Pinotsi, Dorothea; Tunnacliffe, Alan; St. George-Hyslop, Peter; Mandelkow, Eckhard; Mandelkow, Eva-Maria; Kaminski, Clemens F.; Kaminski Schierle, Gabriele S.

    2014-01-01

    Understanding the formation and propagation of aggregates of the Alzheimer disease-associated Tau protein in vivo is vital for the development of therapeutics for this devastating disorder. Using our recently developed live-cell aggregation sensor in neuron-like cells, we demonstrate that different variants of exogenous monomeric Tau, namely full-length Tau (hTau40) and the Tau-derived construct K18 comprising the repeat domain, initially accumulate in endosomal compartments, where they form fibrillar seeds that subsequently induce the aggregation of endogenous Tau. Using superresolution imaging, we confirm that fibrils consisting of endogenous and exogenous Tau are released from cells and demonstrate their potential to spread Tau pathology. Our data indicate a greater pathological risk and potential toxicity than hitherto suspected for extracellular soluble Tau. PMID:24235150

  18. Rescue from tau-induced neuronal dysfunction produces insoluble tau oligomers

    PubMed Central

    Cowan, Catherine M.; Quraishe, Shmma; Hands, Sarah; Sealey, Megan; Mahajan, Sumeet; Allan, Douglas W.; Mudher, Amritpal

    2015-01-01

    Aggregation of highly phosphorylated tau is a hallmark of Alzheimer’s disease and other tauopathies. Nevertheless, animal models demonstrate that tau-mediated dysfunction/toxicity may not require large tau aggregates but instead may be caused by soluble hyper-phosphorylated tau or by small tau oligomers. Challenging this widely held view, we use multiple techniques to show that insoluble tau oligomers form in conditions where tau-mediated dysfunction is rescued in vivo. This shows that tau oligomers are not necessarily always toxic. Furthermore, their formation correlates with increased tau levels, caused intriguingly, by either pharmacological or genetic inhibition of tau kinase glycogen-synthase-kinase-3beta (GSK-3β). Moreover, contrary to common belief, these tau oligomers were neither highly phosphorylated, and nor did they contain beta-pleated sheet structure. This may explain their lack of toxicity. Our study makes the novel observation that tau also forms non-toxic insoluble oligomers in vivo in addition to toxic oligomers, which have been reported by others. Whether these are inert or actively protective remains to be established. Nevertheless, this has wide implications for emerging therapeutic strategies such as those that target dissolution of tau oligomers as they may be ineffective or even counterproductive unless they act on the relevant toxic oligomeric tau species. PMID:26608845

  19. Genome-wide analysis of H4K5 acetylation associated with fear memory in mice

    PubMed Central

    2013-01-01

    Background Histone acetylation has been implicated in learning and memory in the brain, however, its function at the level of the genome and at individual genetic loci remains poorly investigated. This study examines a key acetylation mark, histone H4 lysine 5 acetylation (H4K5ac), genome-wide and its role in activity-dependent gene transcription in the adult mouse hippocampus following contextual fear conditioning. Results Using ChIP-Seq, we identified 23,235 genes in which H4K5ac correlates with absolute gene expression in the hippocampus. However, in the absence of transcription factor binding sites 150 bp upstream of the transcription start site, genes were associated with higher H4K5ac and expression levels. We further establish H4K5ac as a ubiquitous modification across the genome. Approximately one-third of all genes have above average H4K5ac, of which ~15% are specific to memory formation and ~65% are co-acetylated for H4K12. Although H4K5ac is prevalent across the genome, enrichment of H4K5ac at specific regions in the promoter and coding region are associated with different levels of gene expression. Additionally, unbiased peak calling for genes differentially acetylated for H4K5ac identified 114 unique genes specific to fear memory, over half of which have not previously been associated with memory processes. Conclusions Our data provide novel insights into potential mechanisms of gene priming and bookmarking by histone acetylation following hippocampal memory activation. Specifically, we propose that hyperacetylation of H4K5 may prime genes for rapid expression following activity. More broadly, this study strengthens the importance of histone posttranslational modifications for the differential regulation of transcriptional programs in cognitive processes. PMID:23927422

  20. Workshop on Precision Measurements of $\\alpha_s$

    SciTech Connect

    Bethke, Siegfried; Hoang, Andre H.; Kluth, Stefan; Schieck, Jochen; Stewart, Iain W.; Aoki, S.; Beneke, M.; Bethke, S.; Blumlein, J.; Brambilla, N.; Brodsky, S.; /MIT, LNS

    2011-10-01

    These are the proceedings of the Workshop on Precision Measurements of {alpha}{sub s} held at the Max-Planck-Institute for Physics, Munich, February 9-11, 2011. The workshop explored in depth the determination of {alpha}{sub s}(m{sub Z}) in the {ovr MS} scheme from the key categories where high precision measurements are currently being made, including DIS and global PDF fits, {tau}-decays, electro-weak precision observables and Z-decays, event-shapes, and lattice QCD. These proceedings contain a short summary contribution from the speakers, as well as the lists of authors, conveners, participants, and talks.

  1. Reduced CSF p-Tau181 to Tau ratio is a biomarker for FTLD-TDP

    PubMed Central

    Watts, Kelly; Grossman, Murray; Glass, Jonathan; Lah, James J.; Hales, Chadwick; Shelnutt, Matthew; Van Deerlin, Vivianna; Trojanowski, John Q.; Levey, Allan I.

    2013-01-01

    Objectives: To validate the ability of candidate CSF biomarkers to distinguish between the 2 main forms of frontotemporal lobar degeneration (FTLD), FTLD with TAR DNA-binding protein 43 (TDP-43) inclusions (FTLD-TDP) and FTLD with Tau inclusions (FTLD-Tau). Methods: Antemortem CSF samples were collected from 30 patients with FTLD in a single-center validation cohort, and CSF levels of 5 putative FTLD-TDP biomarkers as well as levels of total Tau (t-Tau) and Tau phosphorylated at threonine 181 (p-Tau181) were measured using independent assays. Biomarkers most associated with FTLD-TDP were then tested in a separate 2-center validation cohort composed of subjects with FTLD-TDP, FTLD-Tau, Alzheimer disease (AD), and cognitively normal subjects. The sensitivity and specificity of FTLD-TDP biomarkers were determined. Results: In the first validation cohort, FTLD-TDP cases had decreased levels of p-Tau181 and interleukin-23, and increased Fas. Reduced ratio of p-Tau181 to t-Tau (p/t-Tau) was the strongest predictor of FTLD-TDP pathology. Analysis in the second validation cohort showed CSF p/t-Tau ratio <0.37 to distinguish FTLD-TDP from FTLD-Tau, AD, and healthy seniors with 82% sensitivity and 82% specificity. Conclusion: A reduced CSF p/t-Tau ratio represents a reproducible, validated biomarker for FTLD-TDP with performance approaching well-established CSF AD biomarkers. Introducing this biomarker into research and the clinical arena can significantly increase the power of clinical trials targeting abnormal accumulations of TDP-43 or Tau, and select the appropriate patients for target-specific therapies. Classification of evidence: This study provides Class II evidence that the CSF p/t-Tau ratio distinguishes FTLD-TDP from FTLD-Tau. PMID:24174584

  2. Tau oligomers as potential targets for early diagnosis of tauopathy.

    PubMed

    Sahara, Naruhiko; Ren, Yan; Ward, Sarah; Binder, Lester I; Suhara, Tetsuya; Higuchi, Makoto

    2014-01-01

    The discovery of tau mutations in frontotemporal dementia has been a key event in neurodegenerative disease research. The rTg4510 mouse line expressing human tau with P301L FTDP-17-tau mutation has been established to understand the role of tau in neurodegeneration. Our histological analyses with tau antibodies and fluorescent tau ligands on rTg4510 mice revealed that tau oligomer formation was distinct from tangle formation. While in vivo imaging of mature tangles is now available, imaging biomarkers for tau oligomers would be useful for clarifying their roles in neurotoxicity and for diagnosing early-stage tau pathology. PMID:24595194

  3. Differential induction and spread of tau pathology in young PS19 tau transgenic mice following intracerebral injections of pathological tau from Alzheimer's disease or corticobasal degeneration brains.

    PubMed

    Boluda, Susana; Iba, Michiyo; Zhang, Bin; Raible, Kevin M; Lee, Virginia M-Y; Trojanowski, John Q

    2015-02-01

    Filamentous tau pathologies are hallmark lesions of several neurodegenerative tauopathies including Alzheimer's disease (AD) and corticobasal degeneration (CBD) which show cell type-specific and topographically distinct tau inclusions. Growing evidence supports templated transmission of tauopathies through functionally interconnected neuroanatomical pathways suggesting that different self-propagating strains of pathological tau could account for the diverse manifestations of neurodegenerative tauopathies. Here, we describe the rapid and distinct cell type-specific spread of pathological tau following intracerebral injections of CBD or AD brain extracts enriched in pathological tau (designated CBD-Tau and AD-Tau, respectively) in young human mutant P301S tau transgenic (Tg) mice (line PS19) ~6-9 months before they show onset of mutant tau transgene-induced tau pathology. At 1 month post-injection of CBD-Tau, tau inclusions developed predominantly in oligodendrocytes of the fimbria and white matter near the injection sites with infrequent intraneuronal tau aggregates. In contrast, injections of AD-Tau in young PS19 mice induced tau pathology predominantly in neuronal perikarya with little or no oligodendrocyte involvement 1 month post-injection. With longer post-injection survival intervals of up to 6 months, CBD-Tau- and AD-Tau-induced tau pathology spread to different brain regions distant from the injection sites while maintaining the cell type-specific pattern noted above. Finally, CA3 neuron loss was detected 3 months post-injection of AD-Tau but not CBD-Tau. Thus, AD-Tau and CBD-Tau represent specific pathological tau strains that spread differentially and may underlie distinct clinical and pathological features of these two tauopathies. Hence, these strains could become targets to develop disease-modifying therapies for CBD and AD. PMID:25534024

  4. Increased 4R-Tau Induces Pathological Changes in a Human-Tau Mouse Model.

    PubMed

    Schoch, Kathleen M; DeVos, Sarah L; Miller, Rebecca L; Chun, Seung J; Norrbom, Michaela; Wozniak, David F; Dawson, Hana N; Bennett, C Frank; Rigo, Frank; Miller, Timothy M

    2016-06-01

    Pathological evidence for selective four-repeat (4R) tau deposition in certain dementias and exon 10-positioned MAPT mutations together suggest a 4R-specific role in causing disease. However, direct assessments of 4R toxicity have not yet been accomplished in vivo. Increasing 4R-tau expression without change to total tau in human tau-expressing mice induced more severe seizures and nesting behavior abnormality, increased tau phosphorylation, and produced a shift toward oligomeric tau. Exon 10 skipping could also be accomplished in vivo, providing support for a 4R-tau targeted approach to target 4R-tau toxicity and, in cases of primary MAPT mutation, eliminate the disease-causing mutation. PMID:27210553

  5. Inhibition of tau aggregation by a rosamine derivative that blocks tau intermolecular disulfide cross-linking.

    PubMed

    Haque, Md Mamunul; Kim, Dohee; Yu, Young Hyun; Lim, Sungsu; Kim, Dong Jin; Chang, Young-Tae; Ha, Hyung-Ho; Kim, Yun Kyung

    2014-09-01

    Abnormal tau aggregates are presumed to be neurotoxic and are an important therapeutic target for multiple neurodegenerative disorders including Alzheimer's disease. Growing evidence has shown that tau intermolecular disulfide cross-linking is critical in generating tau oligomers that serve as a building block for higher-order aggregates. Here we report that a small molecule inhibitor prevents tau aggregation by blocking the generation of disulfide cross-linked tau oligomers. Among the compounds tested, a rosamine derivative bearing mild thiol reactivity selectively labeled tau and effectively inhibited oligomerization and fibrillization processes in vitro. Our data suggest that controlling tau oxidation status could be a new therapeutic strategy for prevention of abnormal tau aggregation. PMID:24919397

  6. Tau physics 1994: A theoretical perspective

    SciTech Connect

    Marciano, W.J.

    1994-11-01

    In this paper I describe some recent advances in tau physics and discuss their implications from a theoretical perspective. The examples I have chosen include e-{mu}-{tau} universality, QCD studies, anomalous electroweak dipole moments, and forbidden decays. That list is by no means exhaustive. It should, however, demonstrate the breath of tau physics, describe some interesting new results, and point out the potential for future advances.

  7. Evidence for a tau-neutrino mass

    SciTech Connect

    Samuel, M.A.; Mendel, R.R.

    1988-03-01

    In a recent experiment, the measured lifetime of the tau lepton indicates that the e - ..mu.. universality may not hold in the case of the third-generation leptons. It is shown here that the universality of weak interactions can be restored if the tau-neutrino has a non-zero mass. This results is m/sub v/tau/sub / = (160 +- 70) MeV.

  8. Distinct Therapeutic Mechanisms of Tau Antibodies

    PubMed Central

    Funk, Kristen E.; Mirbaha, Hilda; Jiang, Hong; Holtzman, David M.; Diamond, Marc I.

    2015-01-01

    Tauopathies are neurodegenerative diseases characterized by accumulation of Tau amyloids, and include Alzheimer disease and certain frontotemporal dementias. Trans-neuronal propagation of amyloid mediated by extracellular Tau may underlie disease progression. Consistent with this, active and passive vaccination studies in mouse models reduce pathology, although by unknown mechanisms. We previously reported that intracerebroventricular administration of three anti-Tau monoclonal antibodies (HJ8.5, HJ9.3, and HJ9.4) reduces pathology in a model overexpressing full-length mutant (P301S) human Tau. We now study effects of these three antibodies and a negative control antibody (HJ3.4) on Tau aggregate uptake into BV2 microglial-like cells and primary neurons. Antibody-independent Tau uptake into BV2 cells was blocked by heparin, consistent with a previously described role for heparan sulfate proteoglycans. Two therapeutic antibodies (HJ8.5 and HJ9.4) promoted uptake of full-length Tau fibrils into microglia via Fc receptors. Surprisingly, HJ9.3 promoted uptake of fibrils composed of the Tau repeat domain or Alzheimer disease-derived Tau aggregates, but failed to influence full-length recombinant Tau fibrils. Size fractionation of aggregates showed that antibodies preferentially promote uptake of larger oligomers (n ≥∼20-mer) versus smaller oligomers (n ∼10-mer) or monomer. No antibody inhibited uptake of full-length recombinant fibrils into primary neurons, but HJ9.3 blocked neuronal uptake of Tau repeat domain fibrils and Alzheimer disease-derived Tau. Antibodies thus have multiple potential mechanisms, including clearance via microglia and blockade of neuronal uptake. However these effects are epitope- and aggregate size-dependent. Establishing specific mechanisms of antibody activity in vitro may help in design and optimization of agents that are more effective in vivo. PMID:26126828

  9. Tau Flavour Violation at the LHC

    SciTech Connect

    Carquin, E.

    2009-04-17

    We study the relevance of neutrino oscillation data for sparticle decays that violate the {tau} lepton number at the LHC, in the context of the Constrained Minimal Supersymmetric Extension of the Standard Model (CMSSM) and in SU(5) extensions of the theory. We study the conditions required for {chi}{sub 2}{yields}{chi}+{tau}{sup {+-}}{mu}{sup {+-}} decays to yield observable tau flavour violation, for cosmologically interesting values of the neutralino relic density. We present detailed studies of the relevant supersymmetric parameter space and pay particular emphasis to signals from tau hadronisation, that are analysed using PYTHIA event simulation.

  10. Formation and propagation of tau oligomeric seeds.

    PubMed

    Gerson, Julia E; Kayed, Rakez

    2013-01-01

    Tau misfolding and aggregation leads to the formation of neurofibrillary tangles (NFTs), which have long been considered one of the main pathological hallmarks for numerous neurodegenerative diseases known as tauopathies, including Alzheimer's Disease (AD) and Parkinson's Disease (PD). However, recent studies completed both in vitro and in vivo suggest that intermediate forms of tau, known as tau oligomers, between the monomeric form and NFTs are the true toxic species in disease and the best targets for anti-tau therapies. However, the exact mechanism by which the spread of pathology occurs is unknown. Evidence suggests that tau oligomers may act as templates for the misfolding of native tau, thereby seeding the spread of the toxic forms of the protein. Recently, researchers have reported the ability of tau oligomers to enter and exit cells, propagating from disease-affected regions to unaffected areas. While the mechanism by which the spreading of misfolded tau occurs has yet to be elucidated, there are a few different models which have been proposed, including cell membrane stress and pore-formation, endocytosis and exocytosis, and non-traditional secretion of protein not enclosed by a membrane. Coming to an understanding of how toxic tau species seed and spread through the brain will be crucial to finding effective treatments for neurodegenerative tauopathies. PMID:23882255

  11. Tau regulates the subcellular localization of calmodulin

    SciTech Connect

    Barreda, Elena Gomez de

    2011-05-13

    Highlights: {yields} In this work we have tried to explain how a cytoplasmic protein could regulate a cell nuclear function. We have tested the role of a cytoplasmic protein (tau) in regulating the expression of calbindin gene. We found that calmodulin, a tau-binding protein with nuclear and cytoplasmic localization, increases its nuclear localization in the absence of tau. Since nuclear calmodulin regulates calbindin expression, a decrease in nuclear calmodulin, due to the presence of tau that retains it at the cytoplasm, results in a change in calbindin expression. -- Abstract: Lack of tau expression in neuronal cells results in a change in the expression of few genes. However, little is known about how tau regulates gene expression. Here we show that the presence of tau could alter the subcellular localization of calmodulin, a protein that could be located at the cytoplasm or in the nucleus. Nuclear calmodulin binds to co-transcription factors, regulating the expression of genes like calbindin. In this work, we have found that in neurons containing tau, a higher proportion of calmodulin is present in the cytoplasm compared with neurons lacking tau and that an increase in cytoplasmic calmodulin correlates with a higher expression of calbindin.

  12. Reactive microglia drive tau pathology and contribute to the spreading of pathological tau in the brain

    PubMed Central

    Maphis, Nicole; Xu, Guixiang; Kokiko-Cochran, Olga N.; Jiang, Shanya; Cardona, Astrid; Ransohoff, Richard M.; Lamb, Bruce T.

    2015-01-01

    Pathological aggregation of tau is a hallmark of Alzheimer’s disease and related tauopathies. We have previously shown that the deficiency of the microglial fractalkine receptor (CX3CR1) led to the acceleration of tau pathology and memory impairment in an hTau mouse model of tauopathy. Here, we show that microglia drive tau pathology in a cell-autonomous manner. First, tau hyperphosphorylation and aggregation occur as early as 2 months of age in hTauCx3cr1−/− mice. Second, CD45+ microglial activation correlates with the spatial memory deficit and spread of tau pathology in the anatomically connected regions of the hippocampus. Third, adoptive transfer of purified microglia derived from hTauCx3cr1−/− mice induces tau hyperphosphorylation within the brains of non-transgenic recipient mice. Finally, inclusion of interleukin 1 receptor antagonist (Kineret®) in the adoptive transfer inoculum significantly reduces microglia-induced tau pathology. Together, our results suggest that reactive microglia are sufficient to drive tau pathology and correlate with the spread of pathological tau in the brain. PMID:25833819

  13. Detecting tau in serum of transgenic animal models after tau immunotherapy treatment.

    PubMed

    d'Abramo, Cristina; Acker, Christopher M; Schachter, Joel B; Terracina, Giuseppe; Wang, Xiaohai; Forest, Stefanie K; Davies, Peter

    2016-01-01

    In the attempt to elucidate if the "peripheral sink hypothesis" could be a potential mechanism of action for tau removal in passive immunotherapy experiments, we have examined tau levels in serum of chronically injected JNPL3 and Tg4510 transgenic animals. Measurement of tau in serum of mice treated with tau antibodies is challenging because of the antibody interference in sandwich enzyme-linked immunosorbent assays. To address this issue, we have developed a heat-treatment protocol at acidic pH to remove interfering molecules from serum, with excellent recovery of tau. The present data show that pan-tau and conformational antibodies do increase tau in mouse sera. However, these concentrations in serum do not consistently correlate with reductions of tau pathology in brain, suggesting that large elevations of tau species measured in serum are not predictive of efficacy. Here, we describe a reliable method to detect tau in serum of transgenic animals that have undergone tau immunotherapy. Levels of tau in human serum are less than the sensitivity of current assays, although artifactual signals are common. The method may be useful in similarly treated humans, a situation in which false positive signals are likely. PMID:26508157

  14. Prognostic and Functional Significance of MAP4K5 in Pancreatic Cancer

    PubMed Central

    Wang, Oliver H.; Azizian, Nancy; Guo, Ming; Capello, Michela; Deng, Defeng; Zang, Fenglin; Fry, Jason; Katz, Matthew H.; Fleming, Jason B.; Lee, Jeffrey E.; Wolff, Robert A.; Hanash, Samir; Wang, Huamin; Maitra, Anirban

    2016-01-01

    Objectives MAP4K5 plays an important role in regulating a range of cellular responses and is involved in Wnt signaling in hematopoietic cells. However, its functions in human malignancies have not been studied. The major objectives of this study are to examine the expression, functions and clinical significance of MAP4K5 in pancreatic ductal adenocarcinoma (PDAC). Materials and Methods The expression levels of MAP4K5, E-cadherin, vimentin, and carboxylesterase 2 (CES2) were examined by immunohistochemistry in 105 PDAC and matched non-neoplastic pancreas samples from our institution. The RNA sequencing data of 112 PDAC patients were downloaded from the TCGA data portal. Immunoblotting and RNA sequencing analysis were used to examine the expression of MAP4K5 and E-cadherin in pancreatic cancer cell lines. The effect of knockdown MAP4K5 using siRNA on the expression of CDH1 and vimentin were examined by Real-time RT-PCR in Panc-1 and AsPC-1 cells. Statistical analyses were performed using IBM SPSS Statistics. Results MAP4K5 protein is expressed at high levels specifically in the pancreatic ductal cells of 100% non-neoplastic pancreas samples, but is decreased or lost in 77.1% (81/105) of PDAC samples. MAP4K5-low correlated with the loss of E-cadherin (P = 0.001) and reduced CES2 expression (P = 0.002) in our patient populations. The expression levels of MAP4K5 mRNA directly correlated with the expression levels of CDH1 mRNA (R = 0.2490, P = 0.008) in the second cohort of 112 PDAC patients from The Cancer Genome Atlas (TCGA) RNA-seq dataset. Similar correlations between the expression of MAP4K5 and E-cadherin were observed both at protein and mRNA levels in multiple pancreatic cancer cell lines. Knockdown MAP4K5 led to decreased CDH1 mRNA expression in Panc-1 and AsPC-1 cells. MAP4K5-low correlated significantly with reduced overall survival and was an independent prognosticator in patients with stage II PDAC. Conclusions MAP4K5 expression is decreased or lost in

  15. Selected Topics in Tau Physics from BaBar

    SciTech Connect

    Paramesvaran, S.; /Royal Holloway, U. of London

    2012-04-06

    Selected results from {tau} analyses performed using the BABAR detector at the SLAC National Accelerator Laboratory are presented. A precise measurement of the {tau} mass and the {tau}{sup +}{tau}{sup -} mass difference is undertaken using the hadronic decay mode {tau}{sup {+-}} {yields} {pi}{sup +}{pi}{sup -}{pi}{sup {+-}}{nu}{sub {tau}}. In addition an investigation into the strange decay modes {tau}{sup -} {yields} K{sub S}{sup 0}{pi}{sup -}{pi}{sup 0}{nu}{sub {tau}} and {tau}{sup -} {yields} K{sub S}{sup 0}{pi}{sup -}{nu}{sub {tau}} is also presented, including a fit to the {tau}{sup -} {yields} K{sub S}{sup 0}{pi}{sup -}{nu}{sub {tau}} invariant mass spectrum. Precise values for M(K*(892)) and {Lambda}(K*(892)) are obtained.

  16. The Search for B+ to Tau+ Nu(Tau) at BaBar

    SciTech Connect

    Corwin, L.A.; /SLAC

    2007-01-08

    We present a search for the decay B{sup +} {yields} {tau}{sup +}{nu}{sub {tau}} using 288 fb{sup -1} of data collected at the {Upsilon}(4S) resonance with the BABAR detector at the SLAC PEP-II B-Factory. A sample of events with one reconstructed semileptonic B decay (B{sup -} {yields} D{sup o}{ell}{sup -}{bar {nu}}{sub {ell}}X) is selected, and in the recoil a search for B{sup +} {yields} {tau}{sup +}{nu}{sub {tau}} signal is performed. The {tau} is identified in the following channels: {tau}{sup +} {yields} e{sup +}{nu}{sub e}{bar {nu}}{sub {tau}}, {tau}{sup +} {yields} {mu}{sup +} {nu}{sub {mu}}{bar {nu}}{sub {tau}}, {tau}{sup +} {yields} {pi}{sup +}{pi}{sup 0}{bar {nu}}{sub {tau}}. We measure a branching fraction of {Beta}(B{sup +} {yields} {tau}{sup +}{nu}{sub {tau}}) = 0.88{sub -0.67}{sup +0.68}(stat.) {+-} 0.11(syst.) x 10{sup -4} and extract an upper limit on the branching fraction, at the 90% confidence level, of {Beta}(B{sup +} {yields} {tau}{sup +}{nu}{sub {tau}}) < 1.8 x 10{sup -4}. We calculate the product of the B meson decay constant and |V{sub ub}| to be f{sub B} {center_dot} |V{sub ub}| = (7.0{sub -3.6}{sup +2.3}(stat.){sub -0.5}{sup +0.4}(syst.)) x 10{sup -4} GeV.

  17. Measurement of the Semileptonic Decays B->D tau nu and B->D* tau nu

    SciTech Connect

    Aubert, : B.

    2009-02-23

    The authors present measurements of the semileptonic decays B{sup -} {yields} D{sup 0} {tau}{sup -} {bar {nu}}{sub {tau}}, B{sup -} {yields} D*{sup 0} {tau}{sup -}{bar {nu}}{sub {tau}}, {bar B}{sup 0} {yields} D{sup +} {tau}{sup -} {bar {nu}}{sub {tau}}, and {bar B}{sup 0} {yields} D*{sup +} {tau}{sup -}{bar {nu}}{sub {tau}}, which are sensitive to non-Standard Model amplitudes in certain scenarios. The data sample consists of 232 x 10{sup 6} {Upsilon}(4S) {yields} B{bar B} decays collected with the BABAR detector at the PEP-II e{sup +}e{sup -} collider. They select events with a D or D* meson and a light lepton ({ell} = e or {mu}) recoiling against a fully reconstructed B meson. They perform a fit to the joint distribution of lepton momentum and missing mass squared to distinguish signal B {yields} D{sup (*)}{tau}{sup -} {bar {nu}}{sub {tau}} ({tau}{sup -} {yields} {ell}{sup -} {bar {nu}}{sub {ell}}{nu}{sub {tau}}) events from the backgrounds, predominantly B {yields} D{sup (*)} {ell}{sup -}{bar {nu}}{sub {ell}}. They measure the branching-fraction ratios R(D) {triple_bond} {Beta}(B {yields} D{tau}{sup -} {bar {nu}}{sub {tau}})/{Beta}(B {yields} D{ell}{sup -} {bar {nu}}{sub {ell}}) and R(D*) {triple_bond} {Beta}(B {yields} D*{tau}{sup -} {bar {nu}}{sub {tau}})/{Beta}(B {yields} D* {ell}{sup -} {bar {nu}}{sub {ell}}) and, from a combined fit to B{sup -} and {bar B}{sup 0} channels, obtain the results R(D) = (41.6 {+-} 11.7 {+-} 5.2)% and R(D*) = (29.7 {+-} 5.6 {+-} 1.8)%, where the uncertainties are statistical and systematic. Normalizing to measured B{sup -} {yields} D{sup (*)0} {ell}{sup -} {bar {nu}}{sub {ell}} branching fractions, they obtain {Beta}(B {yields} D{tau}{sup -} {bar {nu}}{sub {tau}}) = (0.86 {+-} 0.24 {+-} 0.11 {+-} 0.06)% and {Beta}(B {yields} D*{tau}{sup -} {bar {nu}}{sub {tau}}) = (1.62 {+-} 0.31 {+-} 0.10 {+-} 0.05)%, where the additional third uncertainty is from the normalization mode. They also present, for the first time, distributions of

  18. Prospect for measuring the CP phase in the $$h\\tau\\tau$$ coupling at the LHC

    DOE PAGESBeta

    Askew, Andrew; Jaiswal, Prerit; Okui, Takemichi; Prosper, Harrison B.; Sato, Nobuo

    2015-04-01

    The search for a new source of CP violation is one of the most important endeavors in particle physics. A particularly interesting way to perform this search is to probe the CP phase in themore » $$h\\tau\\tau$$ coupling, as the phase is currently completely unconstrained by all existing data. Recently, a novel variable $$\\Theta$$ was proposed for measuring the CP phase in the $$h\\tau\\tau$$ coupling through the $$\\tau^\\pm \\to \\pi^\\pm \\pi^0 \

  19. Exclusive branching-fraction measurements of semileptonic tau decays into three charged hadrons, into phipi(-)nu tau, and into phi K(-)nu tau.

    PubMed

    Aubert, B; Bona, M; Boutigny, D; Couderc, F; Karyotakis, Y; Lees, J P; Poireau, V; Tisserand, V; Zghiche, A; Grauges, E; Palano, A; Chen, J C; Qi, N D; Rong, G; Wang, P; Zhu, Y S; Eigen, G; Ofte, I; Stugu, B; Abrams, G S; Battaglia, M; Brown, D N; Button-Shafer, J; Cahn, R N; Charles, E; Gill, M S; Groysman, Y; Jacobsen, R G; Kadyk, J A; Kerth, L T; Kolomensky, Yu G; Kukartsev, G; Pegna, D Lopes; Lynch, G; Mir, L M; Orimoto, T J; Pripstein, M; Roe, N A; Ronan, M T; Wenzel, W A; del Amo Sanchez, P; Barrett, M; Ford, K E; Harrison, T J; Hart, A J; Hawkes, C M; Watson, A T; Held, T; Koch, H; Lewandowski, B; Pelizaeus, M; Peters, K; Schroeder, T; Steinke, M; Boyd, J T; Burke, J P; Cottingham, W N; Walker, D; Asgeirsson, D J; Cuhadar-Donszelmann, T; Fulsom, B G; Hearty, C; Knecht, N S; Mattison, T S; McKenna, J A; Khan, A; Kyberd, P; Saleem, M; Sherwood, D J; Teodorescu, L; Blinov, V E; Bukin, A D; Druzhinin, V P; Golubev, V B; Onuchin, A P; Serednyakov, S I; Skovpen, Yu I; Solodov, E P; Todyshev, K Yu; Best, D S; Bondioli, M; Bruinsma, M; Chao, M; Curry, S; Eschrich, I; Kirkby, D; Lankford, A J; Lund, P; Mandelkern, M; Roethel, W; Stoker, D P; Abachi, S; Buchanan, C; Foulkes, S D; Gary, J W; Long, O; Shen, B C; Wang, K; Zhang, L; Hadavand, H K; Hill, E J; Paar, H P; Rahatlou, S; Sharma, V; Berryhill, J W; Campagnari, C; Cunha, A; Dahmes, B; Hong, T M; Kovalskyi, D; Richman, J D; Beck, T W; Eisner, A M; Flacco, C J; Heusch, C A; Kroseberg, J; Lockman, W S; Nesom, G; Schalk, T; Schumm, B A; Seiden, A; Spradlin, P; Williams, D C; Wilson, M G; Albert, J; Chen, E; Cheng, C H; Dvoretskii, A; Fang, F; Hitlin, D G; Narsky, I; Piatenko, T; Porter, F C; Mancinelli, G; Meadows, B T; Mishra, K; Sokoloff, M D; Blanc, F; Bloom, P C; Chen, S; Ford, W T; Hirschauer, J F; Kreisel, A; Nagel, M; Nauenberg, U; Olivas, A; Ruddick, W O; Smith, J G; Ulmer, K A; Wagner, S R; Zhang, J; Chen, A; Eckhart, E A; Soffer, A; Toki, W H; Wilson, R J; Winklmeier, F; Zeng, Q; Altenburg, D D; Feltresi, E; Hauke, A; Jasper, H; Merkel, J; Petzold, A; Spaan, B; Brandt, T; Klose, V; Lacker, H M; Mader, W F; Nogowski, R; Schubert, J; Schubert, K R; Schwierz, R; Sundermann, J E; Volk, A; Bernard, D; Bonneaud, G R; Latour, E; Thiebaux, Ch; Verderi, M; Clark, P J; Gradl, W; Muheim, F; Playfer, S; Robertson, A I; Xie, Y; Andreotti, M; Bettoni, D; Bozzi, C; Calabrese, R; Cibinetto, G; Luppi, E; Negrini, M; Petrella, A; Piemontese, L; Prencipe, E; Anulli, F; Baldini-Ferroli, R; Calcaterra, A; de Sangro, R; Finocchiaro, G; Pacetti, S; Patteri, P; Peruzzi, I M; Piccolo, M; Rama, M; Zallo, A; Buzzo, A; Contri, R; Lo Vetere, M; Macri, M M; Monge, M R; Passaggio, S; Patrignani, C; Robutti, E; Santroni, A; Tosi, S; Brandenburg, G; Chaisanguanthum, K S; Lee, C L; Morii, M; Wu, J; Dubitzky, R S; Marks, J; Schenk, S; Uwer, U; Bard, D J; Bhimji, W; Bowerman, D A; Dauncey, P D; Egede, U; Flack, R L; Nash, J A; Nikolich, M B; Vazquez, W Panduro; Behera, P K; Chai, X; Charles, M J; Mallik, U; Meyer, N T; Ziegler, V; Cochran, J; Crawley, H B; Dong, L; Eyges, V; Meyer, W T; Prell, S; Rosenberg, E I; Rubin, A E; Gritsan, A V; Denig, A G; Fritsch, M; Schott, G; Arnaud, N; Davier, M; Grosdidier, G; Höcker, A; Lepeltier, V; Le Diberder, F; Lutz, A M; Oyanguren, A; Pruvot, S; Rodier, S; Roudeau, P; Schune, M H; Serrano, J; Stocchi, A; Wang, W F; Wormser, G; Lange, D J; Wright, D M; Chavez, C A; Forster, I J; Fry, J R; Gabathuler, E; Gamet, R; George, K A; Hutchcroft, D E; Payne, D J; Schofield, K C; Touramanis, C; Bevan, A J; Clarke, C K; Di Lodovico, F; Menges, W; Sacco, R; Cowan, G; Flaecher, H U; Hopkins, D A; Jackson, P S; McMahon, T R; Salvatore, F; Wren, A C; Brown, D N; Davis, C L; Allison, J; Barlow, N R; Barlow, R J; Chia, Y M; Edgar, C L; Lafferty, G D; Naisbit, M T; Williams, J C; Yi, J I; Chen, C; Hulsbergen, W D; Jawahery, A; Lae, C K; Roberts, D A; Simi, G; Blaylock, G; Dallapiccola, C; Hertzbach, S S; Li, X; Moore, T B; Saremi, S; Staengle, H; Cowan, R; Sciolla, G; Sekula, S J; Spitznagel, M; Taylor, F; Yamamoto, R K; Kim, H; McLachlin, S E; Patel, P M; Robertson, S H; Lazzaro, A; Lombardo, V; Palombo, F; Bauer, J M; Cremaldi, L; Eschenburg, V; Godang, R; Kroeger, R; Sanders, D A; Summers, D J; Zhao, H W; Brunet, S; Côté, D; Simard, M; Taras, P; Viaud, F B; Nicholson, H; Cavallo, N; De Nardo, G; Fabozzi, F; Gatto, C; Lista, L; Monorchio, D; Paolucci, P; Piccolo, D; Sciacca, C; Baak, M A; Raven, G; Snoek, H L; Jessop, C P; LoSecco, J M; Benelli, G; Corwin, L A; Gan, K K; Honscheid, K; Hufnagel, D; Jackson, P D; Kagan, H; Kass, R; Rahimi, A M; Regensburger, J J; Ter-Antonyan, R; Wong, Q K; Blount, N L; Brau, J; Frey, R; Igonkina, O; Kolb, J A; Lu, M; Potter, C T; Rahmat, R; Sinev, N B; Strom, D; Strube, J; Torrence, E; Gaz, A; Margoni, M; Morandin, M; Pompili, A; Posocco, M; Rotondo, M; Simonetto, F; Stroili, R; Voci, C; Benayoun, M; Briand, H; Chauveau, J; David, P; Del Buono, L; de la Vaissière, Ch; Hamon, O; Hartfiel, B L; Leruste, Ph; Malclès, J; Ocariz, J; Roos, L; Therin, G; Gladney, L; Biasini, M; Covarelli, R; Angelini, C; Batignani, G; Bettarini, S; Bucci, F; Calderini, G; Carpinelli, M; Cenci, R; Forti, F; Giorgi, M A; Lusiani, A; Marchiori, G; Mazur, M A; Morganti, M; Neri, N; Paoloni, E; Rizzo, G; Walsh, J J; Haire, M; Judd, D; Wagoner, D E; Biesiada, J; Danielson, N; Elmer, P; Lau, Y P; Lu, C; Olsen, J; Smith, A J S; Telnov, A V; Bellini, F; Cavoto, G; D'Orazio, A; del Re, D; Di Marco, E; Faccini, R; Ferrarotto, F; Ferroni, F; Gaspero, M; Gioi, L Li; Mazzoni, M A; Morganti, S; Piredda, G; Polci, F; Tehrani, F Safai; Voena, C; Ebert, M; Schröder, H; Waldi, R; Adye, T; Franek, B; Olaiya, E O; Ricciardi, S; Wilson, F F; Aleksan, R; Emery, S; Gaidot, A; Ganzhur, S F; de Monchenault, G Hamel; Kozanecki, W; Legendre, M; Vasseur, G; Yèche, Ch; Zito, M; Chen, X R; Liu, H; Park, W; Purohit, M V; Wilson, J R; Allen, M T; Aston, D; Bartoldus, R; Bechtle, P; Berger, N; Claus, R; Coleman, J P; Convery, M R; Dingfelder, J C; Dorfan, J; Dubois-Felsmann, G P; Dujmic, D; Dunwoodie, W; Field, R C; Glanzman, T; Gowdy, S J; Graham, M T; Grenier, P; Halyo, V; Hast, C; Hryn'ova, T; Innes, W R; Kelsey, M H; Kim, P; Leith, D W G S; Li, S; Luitz, S; Luth, V; Lynch, H L; MacFarlane, D B; Marsiske, H; Messner, R; Muller, D R; O'Grady, C P; Ozcan, V E; Perazzo, A; Perl, M; Pulliam, T; Ratcliff, B N; Roodman, A; Salnikov, A A; Schindler, R H; Schwiening, J; Snyder, A; Stelzer, J; Su, D; Sullivan, M K; Suzuki, K; Swain, S K; Thompson, J M; Va'vra, J; van Bakel, N; Wagner, A P; Weaver, M; Weinstein, A J R; Wisniewski, W J; Wittgen, M; Wright, D H; Wulsin, H W; Yarritu, A K; Yi, K; Young, C C; Burchat, P R; Edwards, A J; Majewski, S A; Petersen, B A; Wilden, L; Ahmed, S; Alam, M S; Bula, R; Ernst, J A; Jain, V; Pan, B; Saeed, M A; Wappler, F R; Zain, S B; Bugg, W; Krishnamurthy, M; Spanier, S M; Eckmann, R; Ritchie, J L; Satpathy, A; Schilling, C J; Schwitters, R F; Izen, J M; Lou, X C; Ye, S; Bianchi, F; Gallo, F; Gamba, D; Bomben, M; Bosisio, L; Cartaro, C; Cossutti, F; Della Ricca, G; Dittongo, S; Lanceri, L; Vitale, L; Azzolini, V; Lopez-March, N; Martinez-Vidal, F; Banerjee, Sw; Bhuyan, B; Brown, C M; Fortin, D; Hamano, K; Kowalewski, R; Nugent, I M; Roney, J M; Sobie, R J; Back, J J; Harrison, P F; Latham, T E; Mohanty, G B; Pappagallo, M; Band, H R; Chen, X; Cheng, B; Dasu, S; Datta, M; Flood, K T; Hollar, J J; Kutter, P E; Mellado, B; Mihalyi, A; Pan, Y; Pierini, M; Prepost, R; Wu, S L; Yu, Z; Neal, H

    2008-01-11

    Using a data sample corresponding to an integrated luminosity of 342 fb(-1) collected with the BABAR detector at the SLAC PEP-II electron-positron storage ring operating at a center-of-mass energy near 10.58 GeV, we measure B(tau(-)--> pi(-)pi(-)pi+nu(tau)(ex.K(S0))=(8.83+/-0.01+/-0.13)%, B(tau(-) -->K(-)pi(-)pi+nu tau(ex.K(S0))=(0.273+/-0.002+/-0.009)%, B(tau(-) -->K(-)pi(-)K+nu tau)=(0.1346+/-0.0010+/-0.0036)%, and B(tau(-) -->K(-)K(-)K+nu tau)=(1.58+/-0.13+/-0.12)x10;{-5}, where the uncertainties are statistical and systematic, respectively. These include significant improvements over previous measurements and a first measurement of B(tau(-) -->K(-)K(-)K+nu tau) in which no resonance structure is assumed. We also report a first measurement of B(tau(-) -->var phi(-)nu tau)=(3.42+/-0.55+/-0.25)x10(-5), a new measurement of B(tau(-) -->var phi K(-)nu tau)=(3.39+/-0.20+/-0.28)x10(-5) and a first upper limit on B(tau(-) -->K(-)K(-)K+nu tau(ex.var phi)). PMID:18232752

  20. Intrinsic Tau Acetylation Is Coupled to Auto-Proteolytic Tau Fragmentation

    PubMed Central

    Cohen, Todd J.; Constance, Brian H.; Hwang, Andrew W.; James, Michael; Yuan, Chao-Xing

    2016-01-01

    Tau proteins are abnormally aggregated in a range of neurodegenerative tauopathies including Alzheimer’s disease (AD). Recently, tau has emerged as an extensively post-translationally modified protein, among which lysine acetylation is critical for normal tau function and its pathological aggregation. Here, we demonstrate that tau isoforms have different propensities to undergo lysine acetylation, with auto-acetylation occurring more prominently within the lysine-rich microtubule-binding repeats. Unexpectedly, we identified a unique intrinsic property of tau in which auto-acetylation induces proteolytic tau cleavage, thereby generating distinct N- and C-terminal tau fragments. Supporting a catalytic reaction-based mechanism, mapping and mutagenesis studies showed that tau cysteines, which are required for acetyl group transfer, are also essential for auto-proteolytic tau processing. Further mass spectrometry analysis identified the C-terminal 2nd and 4th microtubule binding repeats as potential sites of auto-cleavage. The identification of acetylation-mediated auto-proteolysis provides a new biochemical mechanism for tau self-regulation and warrants further investigation into whether auto-catalytic functions of tau are implicated in AD and other tauopathies. PMID:27383765

  1. CHIP-ping away at tau.

    PubMed

    Goryunov, Dmitry; Liem, Ronald K H

    2007-03-01

    Protein accumulation is a hallmark of many neurodegenerative disorders. In Alzheimer's disease (AD), a hyperphosphorylated form of the protein tau (p-tau) forms intracellular inclusions known as neurofibrillary tangles. Deposits of p-tau have also been found in the brains of patients with Down's syndrome, supranuclear palsy, and prion disease. Mutations in tau have been causally associated with at least one inherited neurologic disorder, frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), implying that tau abnormalities by themselves can be a primary cause of degenerative diseases of the CNS. Removal of these p-tau species may occur by both chaperone-mediated refolding and degradation. In this issue of the JCI, Dickey and colleagues show that a cochaperone protein, carboxyl terminus of Hsp70-interacting protein (CHIP), in a complex with Hsp90 plays an important role in the removal of p-tau (see the related article beginning on page 648). Pharmacologic manipulation of Hsp90 may be used to alleviate p-tau accumulation in disease. PMID:17332887

  2. Measurement of tau lepton branching fractions

    SciTech Connect

    Nicol, N.A.

    1993-09-30

    We present {tau}{sup {minus}} lepton branching fraction measurements based on data from the TPC/Two-Gamma detector at PEP. Using a sample of{tau}{sup {minus}} {yields} {nu}{sub {tau}}K{sup {minus}}{pi}{sup +}{pi}{sup {minus}} events, we examine the resonance structure of the K{sup {minus}}{pi}{sup +}{pi}{sup {minus}} system and obtain the first measurements of branching fractions for {tau}{sup {minus}} {yields} {nu}{sub {tau}}K{sub 1}{sup {minus}}(1270) and {tau}{sup {minus}} {yields} {nu}{sub {tau}}K{sub 1}{sup {minus}}(1400). We also describe a complete set of branching fraction measurements in which all the decays of the {tau}{sup {minus}} lepton are separated into classes defined by the identities of the charged particles and an estimate of the number of neutrals. This is the first such global measurement with decay classes defined by the four possible charged particle species, e, {mu}, {pi}, and K.

  3. Physics with tau leptons at CDF

    SciTech Connect

    Hays, C.P.; /Oxford U.

    2007-04-01

    The {radical}s = 1.96 TeV p{bar p} collisions produced by the Tevatron result in many processes with tau leptons in the final state. The CDF Collaboration has studied these final states in Z and t{bar t} production, and has used tau leptons to search for evidence of Higgs, sparticle, and Z{prime} production.

  4. New Features about Tau Function and Dysfunction

    PubMed Central

    Medina, Miguel; Hernández, Félix; Avila, Jesús

    2016-01-01

    Tau is a brain microtubule-associated protein that directly binds to a microtubule and dynamically regulates its structure and function. Under pathological conditions, tau self-assembles into filamentous structures that end up forming neurofibrillary tangles. Prominent tau neurofibrillary pathology is a common feature in a number of neurodegenerative disorders, collectively referred to as tauopathies, the most common of which is Alzheimer’s disease (AD). Beyond its classical role as a microtubule-associated protein, recent advances in our understanding of tau cellular functions have revealed novel insights into their important role during pathogenesis and provided potential novel therapeutic targets. Regulation of tau behavior and function under physiological and pathological conditions is mainly achieved through post-translational modifications, including phosphorylation, glycosylation, acetylation, and truncation, among others, indicating the complexity and variability of factors influencing regulation of tau toxicity, all of which have significant implications for the development of novel therapeutic approaches in various neurodegenerative disorders. A more comprehensive understanding of the molecular mechanisms regulating tau function and dysfunction will provide us with a better outline of tau cellular networking and, hopefully, offer new clues for designing more efficient approaches to tackle tauopathies in the near future. PMID:27104579

  5. New Features about Tau Function and Dysfunction.

    PubMed

    Medina, Miguel; Hernández, Félix; Avila, Jesús

    2016-01-01

    Tau is a brain microtubule-associated protein that directly binds to a microtubule and dynamically regulates its structure and function. Under pathological conditions, tau self-assembles into filamentous structures that end up forming neurofibrillary tangles. Prominent tau neurofibrillary pathology is a common feature in a number of neurodegenerative disorders, collectively referred to as tauopathies, the most common of which is Alzheimer's disease (AD). Beyond its classical role as a microtubule-associated protein, recent advances in our understanding of tau cellular functions have revealed novel insights into their important role during pathogenesis and provided potential novel therapeutic targets. Regulation of tau behavior and function under physiological and pathological conditions is mainly achieved through post-translational modifications, including phosphorylation, glycosylation, acetylation, and truncation, among others, indicating the complexity and variability of factors influencing regulation of tau toxicity, all of which have significant implications for the development of novel therapeutic approaches in various neurodegenerative disorders. A more comprehensive understanding of the molecular mechanisms regulating tau function and dysfunction will provide us with a better outline of tau cellular networking and, hopefully, offer new clues for designing more efficient approaches to tackle tauopathies in the near future. PMID:27104579

  6. Large tau and tau neutrino electric dipole moments in models with vectorlike multiplets

    SciTech Connect

    Ibrahim, Tarek; Nath, Pran

    2010-02-01

    It is shown that the electric dipole moment of the {tau} lepton several orders of magnitude larger than predicted by the standard model can be generated from mixings in models with vectorlike mutiplets. The electric dipole moment (EDM) of the {tau} lepton arises from loops involving the exchange of the W, the charginos, the neutralinos, the sleptons, the mirror leptons, and the mirror sleptons. The EDM of the Dirac {tau} neutrino is also computed from loops involving the exchange of the W, the charginos, the mirror leptons, and the mirror sleptons. A numerical analysis is presented, and it is shown that the EDMs of the {tau} lepton and the {tau} neutrino which lie just a couple of orders of magnitude below the sensitivity of the current experiment can be achieved. Thus the predictions of the model are testable in an improved experiment on the EDM of the {tau} and the {tau} neutrino.

  7. Tau pathology-mediated presynaptic dysfunction.

    PubMed

    Moreno, H; Morfini, G; Buitrago, L; Ujlaki, G; Choi, S; Yu, E; Moreira, J E; Avila, J; Brady, S T; Pant, H; Sugimori, M; Llinás, R R

    2016-06-14

    Brain tauopathies are characterized by abnormal processing of tau protein. While somatodendritic tau mislocalization has attracted considerable attention in tauopathies, the role of tau pathology in axonal transport, connectivity and related dysfunctions remains obscure. We have previously shown using the squid giant synapse that presynaptic microinjection of recombinant human tau protein (htau42) results in failure of synaptic transmission. Here, we evaluated molecular mechanisms mediating this effect. Thus, the initial event, observed after htau42 presynaptic injection, was an increase in transmitter release. This event was mediated by calcium release from intracellular stores and was followed by a reduction in evoked transmitter release. The effect of htau42 on synaptic transmission was recapitulated by a peptide comprising the phosphatase-activating domain of tau, suggesting activation of phosphotransferases. Accordingly, findings indicated that htau42-mediated toxicity involves the activities of both GSK3 and Cdk5 kinases. PMID:27012611

  8. Tau monoclonal antibody generation based on humanized yeast models: impact on Tau oligomerization and diagnostics.

    PubMed

    Rosseels, Joëlle; Van den Brande, Jeff; Violet, Marie; Jacobs, Dirk; Grognet, Pierre; Lopez, Juan; Huvent, Isabelle; Caldara, Marina; Swinnen, Erwin; Papegaey, Anthony; Caillierez, Raphaëlle; Buée-Scherrer, Valerie; Engelborghs, Sebastiaan; Lippens, Guy; Colin, Morvane; Buée, Luc; Galas, Marie-Christine; Vanmechelen, Eugeen; Winderickx, Joris

    2015-02-13

    A link between Tau phosphorylation and aggregation has been shown in different models for Alzheimer disease, including yeast. We used human Tau purified from yeast models to generate new monoclonal antibodies, of which three were further characterized. The first antibody, ADx201, binds the Tau proline-rich region independently of the phosphorylation status, whereas the second, ADx215, detects an epitope formed by the Tau N terminus when Tau is not phosphorylated at Tyr(18). For the third antibody, ADx210, the binding site could not be determined because its epitope is probably conformational. All three antibodies stained tangle-like structures in different brain sections of THY-Tau22 transgenic mice and Alzheimer patients, and ADx201 and ADx210 also detected neuritic plaques in the cortex of the patient brains. In hippocampal homogenates from THY-Tau22 mice and cortex homogenates obtained from Alzheimer patients, ADx215 consistently stained specific low order Tau oligomers in diseased brain, which in size correspond to Tau dimers. ADx201 and ADx210 additionally reacted to higher order Tau oligomers and presumed prefibrillar structures in the patient samples. Our data further suggest that formation of the low order Tau oligomers marks an early disease stage that is initiated by Tau phosphorylation at N-terminal sites. Formation of higher order oligomers appears to require additional phosphorylation in the C terminus of Tau. When used to assess Tau levels in human cerebrospinal fluid, the antibodies permitted us to discriminate patients with Alzheimer disease or other dementia like vascular dementia, indicative that these antibodies hold promising diagnostic potential. PMID:25540200

  9. Reduced number of axonal mitochondria and tau hypophosphorylation in mouse P301L tau knockin neurons

    PubMed Central

    Rodríguez-Martín, Teresa; Pooler, Amy M.; Lau, Dawn H.W.; Mórotz, Gábor M.; De Vos, Kurt J.; Gilley, Jonathan; Coleman, Michael P.; Hanger, Diane P.

    2016-01-01

    Expression of the frontotemporal dementia-related tau mutation, P301L, at physiological levels in adult mouse brain (KI-P301L mice) results in overt hypophosphorylation of tau and age-dependent alterations in axonal mitochondrial transport in peripheral nerves. To determine the effects of P301L tau expression in the central nervous system, we examined the kinetics of mitochondrial axonal transport and tau phosphorylation in primary cortical neurons from P301L knock-in (KI-P301L) mice. We observed a significant 50% reduction in the number of mitochondria in the axons of cortical neurons cultured from KI-P301L mice compared to wild-type neurons. Expression of murine P301L tau did not change the speed, direction of travel or likelihood of movement of mitochondria. Notably, the angle that defines the orientation of the mitochondria in the axon, and the volume of individual moving mitochondria, were significantly increased in neurons expressing P301L tau. We found that murine tau phosphorylation in KI-P301L mouse neurons was diminished and the ability of P301L tau to bind to microtubules was also reduced compared to tau in wild-type neurons. The P301L mutation did not influence the ability of murine tau to associate with membranes in cortical neurons or in adult mouse brain. We conclude that P301L tau is associated with mitochondrial changes and causes an early reduction in murine tau phosphorylation in neurons coupled with impaired microtubule binding of tau. These results support the association of mutant tau with detrimental effects on mitochondria and will be of significance for the pathogenesis of tauopathies. PMID:26459111

  10. Mutant Tau knock-in mice display frontotemporal dementia relevant behaviour and histopathology.

    PubMed

    Koss, David J; Robinson, Lianne; Drever, Benjamin D; Plucińska, Kaja; Stoppelkamp, Sandra; Veselcic, Peter; Riedel, Gernot; Platt, Bettina

    2016-07-01

    Models of Tau pathology related to frontotemporal dementia (FTD) are essential to determine underlying neurodegenerative pathologies and resulting tauopathy relevant behavioural changes. However, existing models are often limited in their translational value due to Tau overexpression, and the frequent occurrence of motor deficits which prevent comprehensive behavioural assessments. In order to address these limitations, a forebrain-specific (CaMKIIα promoter), human mutated Tau (hTauP301L+R406W) knock-in mouse was generated out of the previously characterised PLB1Triple mouse, and named PLB2Tau. After confirmation of an additional hTau species (~60kDa) in forebrain samples, we identified age-dependent progressive Tau phosphorylation which coincided with the emergence of FTD relevant behavioural traits. In line with the non-cognitive symptomatology of FTD, PLB2Tau mice demonstrated early emerging (~6months) phenotypes of heightened anxiety in the elevated plus maze, depressive/apathetic behaviour in a sucrose preference test and generally reduced exploratory activity in the absence of motor impairments. Investigations of cognitive performance indicated prominent dysfunctions in semantic memory, as assessed by social transmission of food preference, and in behavioural flexibility during spatial reversal learning in a home cage corner-learning task. Spatial learning was only mildly affected and task-specific, with impairments at 12months of age in the corner learning but not in the water maze task. Electroencephalographic (EEG) investigations indicated a vigilance-stage specific loss of alpha power during wakefulness at both parietal and prefrontal recording sites, and site-specific EEG changes during non-rapid eye movement sleep (prefrontal) and rapid eye movement sleep (parietal). Further investigation of hippocampal electrophysiology conducted in slice preparations indicated a modest reduction in efficacy of synaptic transmission in the absence of altered synaptic

  11. Characteristics of Tau and Its Ligands in PET Imaging

    PubMed Central

    Harada, Ryuichi; Okamura, Nobuyuki; Furumoto, Shozo; Tago, Tetsuro; Yanai, Kazuhiko; Arai, Hiroyuki; Kudo, Yukitsuka

    2016-01-01

    Tau deposition is one of the neuropathological hallmarks in Alzheimer’s disease as well as in other neurodegenerative disorders called tauopathies. Recent efforts to develop selective tau radiopharmaceuticals have allowed the visualization of tau deposits in vivo. In vivo tau imaging allows the assessment of the regional distribution of tau deposits in a single human subject over time for determining the pathophysiology of tau accumulation in aging and neurodegenerative conditions as well as for application in drug discovery of anti-dementia drugs as surrogate markers. However, tau deposits show complicated characteristics because of different isoform composition, histopathology, and ultrastructure in various neurodegenerative conditions. In addition, since tau radiopharmaceuticals possess different chemotype classes, they may show different binding characteristics with heterogeneous tau deposits. In this review, we describe the characteristics of tau deposits and their ligands that have β-sheet binding properties, and the status of tau imaging in clinical studies. PMID:26751494

  12. Draft Genome Sequence of Escherichia coli Strain Nissle 1917 (Serovar O6:K5:H1).

    PubMed

    Cress, Brady F; Linhardt, Robert J; Koffas, Mattheos A G

    2013-01-01

    We announce the availability of the 5.023-Mbp high-quality draft assembly of the Escherichia coli strain Nissle 1917 (serovar O6:K5:H1) genome. Short genomic segments from this important probiotic strain have been available in public databases, but the full genome sequence has remained inaccessible. Thus, high-coverage, whole genome sequencing of E. coli Nissle 1917 is presented herein. Reannotation and metabolic reconstruction will enable comparative genomics analysis and model-guided predictions of genetic manipulations leading to increased production of the K5 capsular polysaccharide known as N-acetyl heparosan, a precursor to the anticoagulant pharmaceutical heparin. PMID:23516190

  13. K8(K5F)U6Si8O40: An Intergrowth Uranyl Silicate.

    PubMed

    Morrison, Gregory; Tran, T Thao; Halasyamani, P Shiv; Zur Loye, Hans-Conrad

    2016-04-01

    Single crystals of K8(K5F)U6Si8O40 were grown from a mixed alkali halide flux. K8(K5F)U6Si8O40 is the first intergrowth uranyl silicate, being composed of alternating slabs related to two previously reported uranyl silicates: Cs2USiO6 and [Na9F2][(UO2)(UO2)2(Si2O7)2]. It exhibits intense luminescence, which is influenced by the [(UO2)2O] dimers present in the structure. PMID:26974872

  14. Hadronic decays of the tau lepton : {tau}- {yields} ({pi}{pi}{pi})- {nu}{tau} within Resonance Chiral Theory

    SciTech Connect

    Gomez Dumm, D.; Pich, A.; Portoles, J.

    2006-01-12

    {tau} decays into hadrons foresee the study of the hadronization of vector and axial-vector QCD currents, yielding relevant information on the dynamics of the resonances entering into the processes. We analyse {tau} {yields} {pi}{pi}{pi}{nu}{tau} decays within the framework of the Resonance Chiral Theory, comparing this theoretical scheme with the experimental data, namely ALEPH spectral function and branching ratio. Hence we get values for the mass and on-shell width of the a 1 (1260) resonance, and provide the structure functions that have been measured by OPAL and CLEO-II.

  15. Early maturation and distinct tau pathology in induced pluripotent stem cell-derived neurons from patients with MAPT mutations.

    PubMed

    Iovino, Mariangela; Agathou, Sylvia; González-Rueda, Ana; Del Castillo Velasco-Herrera, Martin; Borroni, Barbara; Alberici, Antonella; Lynch, Timothy; O'Dowd, Sean; Geti, Imbisaat; Gaffney, Daniel; Vallier, Ludovic; Paulsen, Ole; Káradóttir, Ragnhildur Thóra; Spillantini, Maria Grazia

    2015-11-01

    Tauopathies, such as Alzheimer's disease, some cases of frontotemporal dementia, corticobasal degeneration and progressive supranuclear palsy, are characterized by aggregates of the microtubule-associated protein tau, which are linked to neuronal death and disease development and can be caused by mutations in the MAPT gene. Six tau isoforms are present in the adult human brain and they differ by the presence of 3(3R) or 4(4R) C-terminal repeats. Only the shortest 3R isoform is present in foetal brain. MAPT mutations found in human disease affect tau binding to microtubules or the 3R:4R isoform ratio by altering exon 10 splicing. We have differentiated neurons from induced pluripotent stem cells derived from fibroblasts of controls and patients with N279K and P301L MAPT mutations. Induced pluripotent stem cell-derived neurons recapitulate developmental tau expression, showing the adult brain tau isoforms after several months in culture. Both N279K and P301L neurons exhibit earlier electrophysiological maturation and altered mitochondrial transport compared to controls. Specifically, the N279K neurons show abnormally premature developmental 4R tau expression, including changes in the 3R:4R isoform ratio and AT100-hyperphosphorylated tau aggregates, while P301L neurons are characterized by contorted processes with varicosity-like structures, some containing both alpha-synuclein and 4R tau. The previously unreported faster maturation of MAPT mutant human neurons, the developmental expression of 4R tau and the morphological alterations may contribute to disease development. PMID:26220942

  16. Early maturation and distinct tau pathology in induced pluripotent stem cell-derived neurons from patients with MAPT mutations

    PubMed Central

    Iovino, Mariangela; Agathou, Sylvia; González-Rueda, Ana; Del Castillo Velasco-Herrera, Martin; Borroni, Barbara; Alberici, Antonella; Lynch, Timothy; O’Dowd, Sean; Geti, Imbisaat; Gaffney, Daniel; Vallier, Ludovic; Paulsen, Ole; Káradóttir, Ragnhildur Thóra

    2015-01-01

    Tauopathies, such as Alzheimer’s disease, some cases of frontotemporal dementia, corticobasal degeneration and progressive supranuclear palsy, are characterized by aggregates of the microtubule-associated protein tau, which are linked to neuronal death and disease development and can be caused by mutations in the MAPT gene. Six tau isoforms are present in the adult human brain and they differ by the presence of 3(3R) or 4(4R) C-terminal repeats. Only the shortest 3R isoform is present in foetal brain. MAPT mutations found in human disease affect tau binding to microtubules or the 3R:4R isoform ratio by altering exon 10 splicing. We have differentiated neurons from induced pluripotent stem cells derived from fibroblasts of controls and patients with N279K and P301L MAPT mutations. Induced pluripotent stem cell-derived neurons recapitulate developmental tau expression, showing the adult brain tau isoforms after several months in culture. Both N279K and P301L neurons exhibit earlier electrophysiological maturation and altered mitochondrial transport compared to controls. Specifically, the N279K neurons show abnormally premature developmental 4R tau expression, including changes in the 3R:4R isoform ratio and AT100-hyperphosphorylated tau aggregates, while P301L neurons are characterized by contorted processes with varicosity-like structures, some containing both alpha-synuclein and 4R tau. The previously unreported faster maturation of MAPT mutant human neurons, the developmental expression of 4R tau and the morphological alterations may contribute to disease development. PMID:26220942

  17. Phosphorylated tau and the neurodegenerative foldopathies.

    PubMed

    Kosik, Kenneth S; Shimura, Hideki

    2005-01-01

    Many studies have implicated phosphorylated tau in the Alzheimer disease process. However, the cellular fate of phosphorylated tau has only recently been described. Recent work has shown that tau phosphorylation at substrate sites for the kinases Cdk5 and GSK3-beta can trigger the binding of tau to the chaperones Hsc70 and Hsp27. The binding of phosphorylated tau to Hsc70 implied that the complex may be a substrate for the E3 ligase CHIP and this possibility was experimentally verified. The presence of this system in cells suggests that phosphorylated tau may hold toxic dangers for cell viability, and the response of the cell is to harness a variety of protective mechanisms. These include binding to chaperones, which may prevent more toxic conformations of the protein, ubiquitination which will direct the protein to the proteasome, segregation of tau aggregates from the cellular machinery, and recruitment of Hsp27 which will confer anti-apoptotic properties to the cell. PMID:15615647

  18. Science IDEAS: A Research-Based K-5 Interdisciplinary Instructional Model Linking Science and Literacy

    ERIC Educational Resources Information Center

    Romance, Nancy R.; Vitale, Michael R.

    2012-01-01

    Science IDEAS is an evidence-based model that reflects interdisciplinary research findings that support the integration of literacy (e.g., reading comprehension) within science instruction in grades K-5. Presented is a framework for planning integrated science and literacy instruction in which six elements (hands-on investigations, reading,…

  19. Mobile Devices and the Teacher Perceived Barriers Impacting Effective Integration in the K-5 Classroom

    ERIC Educational Resources Information Center

    Nixon, Tina S.

    2013-01-01

    This qualitative, phenomenological study explored the teacher perceived barriers of using mobile devices in the K-5 classroom. Research confirms teachers face various types of variables and become reluctant to use technology within their curriculum driven lessons. This study sought to understand what teachers perceive as barriers, and how the…

  20. K-5 Student Experiences in a Dance Residency: A Case Study

    ERIC Educational Resources Information Center

    Leonard, Alison E.; McShane-Hellenbrand, Karen

    2012-01-01

    In this article, the collaborating authors, a researcher and dance artist, confront assumptions surrounding dance's experiential nature and assessment in schools. Presenting findings from a qualitative case study assessment of a three-week, whole-school dance artist-in-residence at a diverse and inclusive metropolitan K-5 school, the authors focus…

  1. Perceptions of Stress among Native American and Hispanic K-5 Teachers

    ERIC Educational Resources Information Center

    Lotz-Drlik, Jane Elizabeth

    2012-01-01

    Within the context of a nationwide shortage of teachers of color, stable enrollment of Native American students, and increasing enrollments of Hispanic students, the purpose of this study was to examine self-reported stress among Native American, Hispanic, and Caucasian K-5 teachers. This was a mixed-methods study, with both quantitative and…

  2. Students' Stories of Their Best and Poorest K-5 Teachers: A Mixed Data Analysis

    ERIC Educational Resources Information Center

    Slate, John R.; Capraro, Mary Margaret; Onwuegbuzie, Anthony J.

    2007-01-01

    In this study, a multi-stage mixed analysis was used to examine stories from 72 undergraduate teacher education students regarding their best and poorest K-5 teachers, alongside responses to Likert-format survey items. Participants expressed strong agreement with items derived from the literature concerning characteristics of effective teachers…

  3. Social Studies: Standards, End of Grade Cluster Benchmarks, Performance Indicators. Grades K-5. Revised.

    ERIC Educational Resources Information Center

    Delaware State Dept. of Public Instruction, Dover.

    This Delaware state content standards booklet for teaching grades K-5 social studies in Delaware public schools begins with a one page chart outlining information for the disciplines of civics, economics, geography, and U.S. history. The booklet addresses standards for civics, lists end of cluster expectations for the end of grade three and the…

  4. Language Assessment Scales, LAS I, for Grades K-5, English/Spanish. Second Edition.

    ERIC Educational Resources Information Center

    De Avila, Edward A.; Duncan, Sharon E.

    Language Assessment Scales, LAS I, are designed for children in grades K-5. LAS I accommodates ethnic and linguistic differences and provides direct language activities taken from the popular culture of both English- and Spanish-speaking peoples. LAS I consists of two independent tests, one in English and the other in Spanish, presented largely on…

  5. Stress Education Curriculum: Grades K-5, Elementary School Level. Fourth Edition.

    ERIC Educational Resources Information Center

    Trotter, Jennie C.

    Stress is an inevitable part of living, but too much stress can have damaging consequences. Ways in which children can respond positively to stress are covered in this curriculum guide. It was developed to help teachers teach students, grades K-5, ways to cope with stress. Its curriculum objectives include helping students understand stress and…

  6. Native American (K-5) and Math (9 - 12 ) Astronomy Lessons Plans.

    NASA Astrophysics Data System (ADS)

    Canterna, Ronald W.; Singer, E.; Hoffman, J.

    2007-12-01

    As part of the education component of the Wyoming RET program astronomy lesson plans were developed for elementary and senior HS students. E. Singer developed a thematic unit for grades K-5 based on Native American astronomy. J Hoffman developed lesson plans for high school (9-12) math classes based on astronomy topics. Both plans will be present.

  7. Democratic Bodies: Exemplary Practice and Democratic Education in a K-5 Dance Residency

    ERIC Educational Resources Information Center

    Leonard, Alison E.

    2014-01-01

    This research highlights a K-5 dance artist-in-residence as a form of democratic and exemplary dance education that ignited collaboration, promoted equity, fostered student autonomy, and demonstrated rigor in school curriculum. Through examining observation, interview, and performance-based data and calling upon critical, democratic education…

  8. Tensor mesons produced in tau lepton decays

    SciTech Connect

    Lopez Castro, G.; Munoz, J. H.

    2011-05-01

    Light tensor mesons (T=a{sub 2}, f{sub 2} and K{sub 2}*) can be produced in decays of {tau} leptons. In this paper we compute the branching ratios of {tau}{yields}T{pi}{nu} decays by assuming the dominance of intermediate virtual states to model the form factors involved in the relevant hadronic matrix elements. The exclusive f{sub 2}(1270){pi}{sup -} decay mode turns out to have the largest branching ratio, of O(10{sup -4}). Our results indicate that the contribution of tensor meson intermediate states to the three-pseudoscalar channels of {tau} decays are rather small.

  9. Precision measurements of tau lepton decays

    NASA Astrophysics Data System (ADS)

    Nugent, Ian M.

    Using data collected with the BABAR detector at the SLAC PEP-II electron-positron storage ring operating at a centre-of-mass energy near 10.58 GeV, the branching fractions B (tau-- → pi--pi --pi+nutau) = (8.83 +/- 0.01 +/- 0.13)%, B (tau-- → K--pi --pi+nutau) = (0.273 +/- 0.002 +/- 0.009)%, B (tau-- → K--pi --K+nutau) = (0.1346 +/- 0.0010 +/- 0.0036)%, and B (tau-- → K-- K--K +nutau) = (1.58 +/- 0.13 +/- 0.12) x 10--5 are measured where the uncertainties are statistical and systematic, respectively. The invariant mass distribution for the tau -- → pi--pi--pi +nutau, tau-- → K--pi--pi+nu tau, tau-- → K --pi--K+nu tau and tau-- → K --K--K +nutau decays are unfolded to correct for detector effects. A measurement of B (tau-- → φpi--nu tau) = (3.42 +/- 0.55 +/- 0.25) x 10--5 , a measurement of B (tau-- → φK --nutau) = (3.39 +/- 0.20 +/- 0.28) x 10--5 and an upper limit on B (tau-- → K-- K--K +nutau [ex.φ]) ≤ 2.5 x 10--6 90%CL are determined from a binned maximum likelihood fit of the tau-- → K-- pi--K+nu tau and tau-- → K --K--K +nutau K+K -- invariant mass distributions. The branching ratio Bt-→K -nt Bt-→p -nt is measured to be (6.531 +/- 0.056 +/- 0.093) x 10 --2 from which |Vus| is determined to be 0.2255 +/- 0.0023. The branching ratio Bt-→m -ntn¯ mB t-→e-nt n¯e = (9.796 +/- 0.016 +/- 0.035) x 10--1 is measured enabling a precision test of the Standard Model assumption of charged current lepton universality, gmge = 1.0036 +/- 0.0020. The branching ratios Bt-→K -nt Bt-→e- ntn¯ e = (3.882 +/- 0.032 +/- 0.056) x 10--2 , and Bt-→p -nt Bt-→e- ntn¯ e = (5.945 +/- 0.014 +/- 0.061) x 10--1 are measured which provide additional tests of charged current lepton universality, gtgm p = 0.9856 +/- 0.0057 and gtgm K = 0.9827 +/- 0.0086 which can be combined to give gtgm p/K = 0.9850 +/- 0.0054. Any deviation of these measurements from the expected Standard Model values would be an indication of new physics.

  10. FTDP-17 tau mutations decrease the susceptibility of tau to calpain I digestion.

    PubMed

    Yen, S; Easson, C; Nacharaju, P; Hutton, M; Yen, S H

    1999-11-12

    Frontal temporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17) is caused by splice site and missense mutations in the tau gene, and characterized by the accumulation of filamentous tau in cerebral neurons and glia. The missense mutations reduce the ability of tau to promote microtubule assembly and increase the ability of tau to form filaments. In this report we demonstrate that mutants V337M and R406W are less susceptible than mutant P301L or corresponding wild type tau to degradation by calpain I. The differences were at least in part due to changes in accessibility of a cleavage site located about 100 amino acids off the carboxy-terminus. The results suggest that the pathogenesis of some forms of FTDP-17 may involve tau accumulation due to decreased proteolytic degradation. PMID:10561502

  11. Measurement of the Tau Lepton Lifetime at Opal

    NASA Astrophysics Data System (ADS)

    Janissen, Anna Cornelia

    1993-01-01

    This thesis describes a new measurement of the tau (tau) lepton lifetime using two statistically independent techniques each associated with one of the two principle decay topologies of the tau to one and three charged particles, respectively. The measurement was performed with data collected in 1990 and 1991 at the OPAL detector at the LEP e^+e ^- colliding beam accelerator at CERN. The LEP collider operates at a significantly higher energy than previous e^+e^- colliders. This presents a new experimental opportunity to investigate the physics associated with the tau<=pton in general and the tau lifetime in particular. The tau lepton is one of three similar electron -like particles: e, mu, and tau. These leptons exhibit a hierarchy of masses with: m_{e} < m_ {mu} < m_{tau}. While the electron is stable, the mu and the tau are unstable and decay via the weak interaction charged current. It is a fundamental feature of the standard model of fundamental particles and their interactions that this weak charged current has exactly the same strength for each of the three leptons; a phenomenon called lepton universality. The tau lifetime, tau_tau, can be related to the mu lifetime, tau_ mu, and the average leptonic branching ratio, BR(tau to lnu| nu), by:tau_ tau = tau_mu {G_mu G_{e}over G_tau G_ l} ({m_muover m_tau})^5 {rm BR}(tautolnu|nu)R where R is a calculable factor to account for phase space and radiative corrections, and G _l is the Fermi effective coupling strength of the weak charged current to the lepton l. Lepton universality implies that G _mu = G_{e} = G_tau. The experimentally measured tau lifetime, together with the measurements of the other quantities in the above relation, can be interpreted as a direct test of lepton universality. The tau lifetime measured with each of the two independent techniques is: eqalign{tau_1 &rm= 296.4+/-7.1(stat.)+/- 3.8(sys.) fscr tau_3 &rm= 286.3+/-7.4(stat.)+/-5.2(sys.) fs.}The systematic uncertainties for each of the

  12. Search for second-class currents in tau;{-} --> omegapi;{-}nu_{tau}.

    PubMed

    Aubert, B; Karyotakis, Y; Lees, J P; Poireau, V; Prencipe, E; Prudent, X; Tisserand, V; Tico, J Garra; Grauges, E; Martinelli, M; Palano, A; Pappagallo, M; Eigen, G; Stugu, B; Sun, L; Battaglia, M; Brown, D N; Kerth, L T; Kolomensky, Yu G; Lynch, G; Osipenkov, I L; Tackmann, K; Tanabe, T; Hawkes, C M; Soni, N; Watson, A T; Koch, H; Schroeder, T; Asgeirsson, D J; Fulsom, B G; Hearty, C; Mattison, T S; McKenna, J A; Barrett, M; Khan, A; Randle-Conde, A; Blinov, V E; Bukin, A D; Buzykaev, A R; Druzhinin, V P; Golubev, V B; Onuchin, A P; Serednyakov, S I; Skovpen, Yu I; Solodov, E P; Todyshev, K Yu; Bondioli, M; Curry, S; Eschrich, I; Kirkby, D; Lankford, A J; Lund, P; Mandelkern, M; Martin, E C; Stoker, D P; Atmacan, H; Gary, J W; Liu, F; Long, O; Vitug, G M; Yasin, Z; Zhang, L; Sharma, V; Campagnari, C; Hong, T M; Kovalskyi, D; Mazur, M A; Richman, J D; Beck, T W; Eisner, A M; Heusch, C A; Kroseberg, J; Lockman, W S; Martinez, A J; Schalk, T; Schumm, B A; Seiden, A; Wang, L; Winstrom, L O; Cheng, C H; Doll, D A; Echenard, B; Fang, F; Hitlin, D G; Narsky, I; Piatenko, T; Porter, F C; Andreassen, R; Mancinelli, G; Meadows, B T; Mishra, K; Sokoloff, M D; Bloom, P C; Ford, W T; Gaz, A; Hirschauer, J F; Nagel, M; Nauenberg, U; Smith, J G; Wagner, S R; Ayad, R; Toki, W H; Wilson, R J; Feltresi, E; Hauke, A; Jasper, H; Karbach, T M; Merkel, J; Petzold, A; Spaan, B; Wacker, K; Kobel, M J; Nogowski, R; Schubert, K R; Schwierz, R; Volk, A; Bernard, D; Latour, E; Verderi, M; Clark, P J; Playfer, S; Watson, J E; Andreotti, M; Bettoni, D; Bozzi, C; Calabrese, R; Cecchi, A; Cibinetto, G; Fioravanti, E; Franchini, P; Luppi, E; Munerato, M; Negrini, M; Petrella, A; Piemontese, L; Santoro, V; Baldini-Ferroli, R; Calcaterra, A; de Sangro, R; Finocchiaro, G; Pacetti, S; Patteri, P; Peruzzi, I M; Piccolo, M; Rama, M; Zallo, A; Contri, R; Guido, E; Lo Vetere, M; Monge, M R; Passaggio, S; Patrignani, C; Robutti, E; Tosi, S; Chaisanguanthum, K S; Morii, M; Adametz, A; Marks, J; Schenk, S; Uwer, U; Bernlochner, F U; Klose, V; Lacker, H M; Bard, D J; Dauncey, P D; Tibbetts, M; Behera, P K; Charles, M J; Mallik, U; Cochran, J; Crawley, H B; Dong, L; Eyges, V; Meyer, W T; Prell, S; Rosenberg, E I; Rubin, A E; Gao, Y Y; Gritsan, A V; Guo, Z J; Arnaud, N; Béquilleux, J; D'Orazio, A; Davier, M; Derkach, D; da Costa, J Firmino; Grosdidier, G; Le Diberder, F; Lepeltier, V; Lutz, A M; Malaescu, B; Pruvot, S; Roudeau, P; Schune, M H; Serrano, J; Sordini, V; Stocchi, A; Wormser, G; Lange, D J; Wright, D M; Bingham, I; Burke, J P; Chavez, C A; Fry, J R; Gabathuler, E; Gamet, R; Hutchcroft, D E; Payne, D J; Touramanis, C; Bevan, A J; Clarke, C K; Di Lodovico, F; Sacco, R; Sigamani, M; Cowan, G; Paramesvaran, S; Wren, A C; Brown, D N; Davis, C L; Denig, A G; Fritsch, M; Gradl, W; Hafner, A; Alwyn, K E; Bailey, D; Barlow, R J; Jackson, G; Lafferty, G D; West, T J; Yi, J I; Anderson, J; Chen, C; Jawahery, A; Roberts, D A; Simi, G; Tuggle, J M; Dallapiccola, C; Salvati, E; Saremi, S; Cowan, R; Dujmic, D; Fisher, P H; Henderson, S W; Sciolla, G; Spitznagel, M; Yamamoto, R K; Zhao, M; Patel, P M; Robertson, S H; Schram, M; Lazzaro, A; Lombardo, V; Palombo, F; Stracka, S; Bauer, J M; Cremaldi, L; Godang, R; Kroeger, R; Sonnek, P; Summers, D J; Zhao, H W; Simard, M; Taras, P; Nicholson, H; De Nardo, G; Lista, L; Monorchio, D; Onorato, G; Sciacca, C; Raven, G; Snoek, H L; Jessop, C P; Knoepfel, K J; Losecco, J M; Wang, W F; Corwin, L A; Honscheid, K; Kagan, H; Kass, R; Morris, J P; Rahimi, A M; Regensburger, J J; Sekula, S J; Wong, Q K; Blount, N L; Brau, J; Frey, R; Igonkina, O; Kolb, J A; Lu, M; Rahmat, R; Sinev, N B; Strom, D; Strube, J; Torrence, E; Castelli, G; Gagliardi, N; Margoni, M; Morandin, M; Posocco, M; Rotondo, M; Simonetto, F; Stroili, R; Voci, C; Del Amo Sanchez, P; Ben-Haim, E; Bonneaud, G R; Briand, H; Chauveau, J; Hamon, O; Leruste, Ph; Marchiori, G; Ocariz, J; Perez, A; Prendki, J; Sitt, S; Gladney, L; Biasini, M; Manoni, E; Angelini, C; Batignani, G; Bettarini, S; Calderini, G; Carpinelli, M; Cervelli, A; Forti, F; Giorgi, M A; Lusiani, A; Morganti, M; Neri, N; Paoloni, E; Rizzo, G; Walsh, J J; Pegna, D Lopes; Lu, C; Olsen, J; Smith, A J S; Telnov, A V; Anulli, F; Baracchini, E; Cavoto, G; Faccini, R; Ferrarotto, F; Ferroni, F; Gaspero, M; Jackson, P D; Gioi, L Li; Mazzoni, M A; Morganti, S; Piredda, G; Renga, F; Voena, C; Ebert, M; Hartmann, T; Schröder, H; Waldi, R; Adye, T; Franek, B; Olaiya, E O; Wilson, F F; Emery, S; Esteve, L; de Monchenault, G Hamel; Kozanecki, W; Vasseur, G; Yèche, Ch; Zito, M; Allen, M T; Aston, D; Bartoldus, R; Benitez, J F; Cenci, R; Coleman, J P; Convery, M R; Dingfelder, J C; Dorfan, J; Dubois-Felsmann, G P; Dunwoodie, W; Field, R C; Sevilla, M Franco; Gabareen, A M; Graham, M T; Grenier, P; Hast, C; Innes, W R; Kaminski, J; Kelsey, M H; Kim, H; Kim, P; Kocian, M L; Leith, D W G S; Li, S; Lindquist, B; Luitz, S; Luth, V; Lynch, H L; Macfarlane, D B; Marsiske, H; Messner, R; Muller, D R; Neal, H; Nelson, S; O'Grady, C P; Ofte, I; Perl, M; Ratcliff, B N; Roodman, A; Salnikov, A A; Schindler, R H; Schwiening, J; Snyder, A; Su, D; Sullivan, M K; Suzuki, K; Swain, S K; Thompson, J M; Va'vra, J; Wagner, A P; Weaver, M; West, C A; Wisniewski, W J; Wittgen, M; Wright, D H; Wulsin, H W; Yarritu, A K; Young, C C; Ziegler, V; Chen, X R; Liu, H; Park, W; Purohit, M V; White, R M; Wilson, J R; Burchat, P R; Edwards, A J; Miyashita, T S; Ahmed, S; Alam, M S; Ernst, J A; Pan, B; Saeed, M A; Zain, S B; Soffer, A; Spanier, S M; Wogsland, B J; Eckmann, R; Ritchie, J L; Ruland, A M; Schilling, C J; Schwitters, R F; Wray, B C; Drummond, B W; Izen, J M; Lou, X C; Bianchi, F; Gamba, D; Pelliccioni, M; Bomben, M; Bosisio, L; Cartaro, C; Della Ricca, G; Lanceri, L; Vitale, L; Azzolini, V; Lopez-March, N; Martinez-Vidal, F; Milanes, D A; Oyanguren, A; Albert, J; Banerjee, Sw; Bhuyan, B; Choi, H H F; Hamano, K; King, G J; Kowalewski, R; Lewczuk, M J; Nugent, I M; Roney, J M; Sobie, R J; Gershon, T J; Harrison, P F; Ilic, J; Latham, T E; Mohanty, G B; Puccio, E M T; Band, H R; Chen, X; Dasu, S; Flood, K T; Pan, Y; Prepost, R; Vuosalo, C O; Wu, S L

    2009-07-24

    We report an analysis of tau;{-} decaying into omegapi;{-}nu_{tau} with omega --> pi;{+}pi;{-}pi;{0} using a data sample containing nearly 320 x 10;{6}tau pairs collected with the BABAR detector at the PEP-II B-Factory. We find no evidence for second-class currents, and we set an upper limit of 0.69% at 90% confidence level for the fraction of second-class currents in this decay mode. PMID:19659341

  13. Search for the rare decay B0-->tau+tau- at BABAR.

    PubMed

    Aubert, B; Barate, R; Boutigny, D; Couderc, F; Karyotakis, Y; Lees, J P; Poireau, V; Tisserand, V; Zghiche, A; Grauges, E; Palano, A; Pappagallo, M; Pompili, A; Chen, J C; Qi, N D; Rong, G; Wang, P; Zhu, Y S; Eigen, G; Ofte, I; Stugu, B; Abrams, G S; Battaglia, M; Breon, A B; Brown, D N; Button-Shafer, J; Cahn, R N; Charles, E; Day, C T; Gill, M S; Gritsan, A V; Groysman, Y; Jacobsen, R G; Kadel, R W; Kadyk, J; Kerth, L T; Kolomensky, Yu G; Kukartsev, G; Lynch, G; Mir, L M; Oddone, P J; Orimoto, T J; Pripstein, M; Roe, N A; Ronan, M T; Wenzel, W A; Barrett, M; Ford, K E; Harrison, T J; Hart, A J; Hawkes, C M; Morgan, S E; Watson, A T; Fritsch, M; Goetzen, K; Held, T; Koch, H; Lewandowski, B; Pelizaeus, M; Peters, K; Schroeder, T; Steinke, M; Boyd, J T; Burke, J P; Chevalier, N; Cottingham, W N; Cuhadar-Donszelmann, T; Fulsom, B G; Hearty, C; Knecht, N S; Mattison, T S; McKenna, J A; Khan, A; Kyberd, P; Saleem, M; Teodorescu, L; Blinov, A E; Blinov, V E; Bukin, A D; Druzhinin, V P; Golubev, V B; Kravchenko, E A; Onuchin, A P; Serednyakov, S I; Skovpen, Yu I; Solodov, E P; Yushkov, A N; Best, D; Bondioli, M; Bruinsma, M; Chao, M; Curry, S; Eschrich, I; Kirkby, D; Lankford, A J; Lund, P; Mandelkern, M; Mommsen, R K; Roethel, W; Stoker, D P; Buchanan, C; Hartfiel, B L; Weinstein, A J R; Foulkes, S D; Gary, J W; Long, O; Shen, B C; Wang, K; Zhang, L; del Re, D; Hadavand, H K; Hill, E J; MacFarlane, D B; Paar, H P; Rahatlou, S; Sharma, V; Berryhill, J W; Campagnari, C; Cunha, A; Dahmes, B; Hong, T M; Mazur, M A; Richman, J D; Verkerke, W; Beck, T W; Eisner, A M; Flacco, C J; Heusch, C A; Kroseberg, J; Lockman, W S; Nesom, G; Schalk, T; Schumm, B A; Seiden, A; Spradlin, P; Williams, D C; Wilson, M G; Albert, J; Chen, E; Dubois-Felsmann, G P; Dvoretskii, A; Hitlin, D G; Narsky, I; Piatenko, T; Porter, F C; Ryd, A; Samuel, A; Andreassen, R; Mancinelli, G; Meadows, B T; Sokoloff, M D; Blanc, F; Bloom, P; Chen, S; Ford, W T; Hirschauer, J F; Kreisel, A; Nauenberg, U; Olivas, A; Rankin, P; Ruddick, W O; Smith, J G; Ulmer, K A; Wagner, S R; Zhang, J; Chen, A; Eckhart, E A; Harton, J L; Soffer, A; Toki, W H; Wilson, R J; Zeng, Q; Aleksan, R; Emery, S; Gaidot, A; Ganzhur, S F; Giraud, P-F; Graziani, G; Hamel de Monchenault, G; Kozanecki, W; Legendre, M; London, G W; Mayer, B; Vasseur, G; Yeche, Ch; Zito, M; Altenburg, D; Feltresi, E; Hauke, A; Spaan, B; Brandt, T; Brose, J; Dickopp, M; Klose, V; Lacker, H M; Nogowski, R; Otto, S; Petzold, A; Schubert, J; Schubert, K R; Schwierz, R; Sundermann, J E; Bernard, D; Bonneaud, G R; Grenier, P; Schrenk, S; Thiebaux, Ch; Vasileiadis, G; Verderi, M; Bard, D J; Clark, P J; Gradl, W; Muheim, F; Playfer, S; Xie, Y; Andreotti, M; Azzolini, V; Bettoni, D; Bozzi, C; Calabrese, R; Cibinetto, G; Luppi, E; Negrini, M; Piemontese, L; Anulli, F; Baldini-Ferroli, R; Calcaterra, A; de Sangro, R; Finocchiaro, G; Patteri, P; Peruzzi, I M; Piccolo, M; Zallo, A; Buzzo, A; Capra, R; Contri, R; Lo Vetere, M; Macri, M; Monge, M R; Passaggio, S; Patrignani, C; Robutti, E; Santroni, A; Tosi, S; Brandenburg, G; Chaisanguanthum, K S; Morii, M; Won, E; Wu, J; Dubitzky, R S; Langenegger, U; Marks, J; Schenk, S; Uwer, U; Martinez-Vidal, F; Bhimji, W; Bowerman, D A; Dauncey, P D; Egede, U; Flack, R L; Gaillard, J R; Morton, G W; Nash, J A; Nikolich, M B; Taylor, G P; Vazquez, W P; Charles, M J; Mader, W F; Mallik, U; Mohapatra, A K; Cochran, J; Crawley, H B; Eyges, V; Meyer, W T; Prell, S; Rosenberg, E I; Rubin, A E; Yi, J; Biasini, M; Covarelli, R; Pacetti, S; Pioppi, M; Arnaud, N; Davier, M; Giroux, X; Grosdidier, G; Höcker, A; Le Diberder, F; Lepeltier, V; Lutz, A M; Oyanguren, A; Petersen, T C; Pierini, M; Plaszczynski, S; Rodier, S; Roudeau, P; Schune, M H; Stocchi, A; Wormser, G; Cheng, C H; Lange, D J; Simani, M C; Wright, D M; Bevan, A J; Chavez, C A; Forster, Ian J; Fry, J R; Gabathuler, E; Gamet, R; George, K A; Hutchcroft, D E; Parry, R J; Payne, D J; Schofield, K C; Touramanis, C; Cormack, C M; Di Lodovico, F; Menges, W; Sacco, R; Brown, C L; Cowan, G; Flaecher, H U; Green, M G; Hopkins, D A; Jackson, P S; McMahon, T R; Ricciardi, S; Salvatore, F; Brown, D; Davis, C L; Allison, J; Barlow, N R; Barlow, R J; Edgar, C L; Hodgkinson, M C; Kelly, M P; Lafferty, G D; Naisbit, M T; Williams, J C; Chen, C; Hulsbergen, W D; Jawahery, A; Kovalskyi, D; Lae, C K; Roberts, D A; Simi, G; Blaylock, G; Dallapiccola, C; Hertzbach, S S; Kofler, R; Koptchev, V B; Li, X; Moore, T B; Saremi, S; Staengle, H; Willocq, S; Cowan, R; Koeneke, K; Sciolla, G; Sekula, S J; Spitznagel, M; Taylor, F; Yamamoto, R K; Kim, H; Patel, P M; Robertson, S H; Lazzaro, A; Lombardo, V; Palombo, F; Bauer, J M; Cremaldi, L; Eschenburg, V; Godang, R; Kroeger, R; Reidy, J; Sanders, D A; Summers, D J; Zhao, H W; Brunet, S; Cote, D; Taras, P; Viaud, B; Nicholson, H; Baak, M; Bulten, H; Raven, G; Snoek, H L; Wilden, L; Cavallo, N; De Nardo, G; Fabozzi, F; Gatto, C; Lista, L; Monorchio, D; Paolucci, P; Piccolo, D; Sciacca, C; Jessop, C P; LoSecco, J M; Allmendinger, T; Benelli, G; Gan, K K; Honscheid, K; Hufnagel, D; Jackson, P D; Kagan, H; Kass, R; Pulliam, T; Rahimi, A M; Ter-Antonyan, R; Wong, Q K; Brau, J; Frey, R; Igonkina, O; Lu, M; Potter, C T; Sinev, N B; Strom, D; Strube, J; Torrence, E; Galeazzi, F; Margoni, M; Morandin, M; Posocco, M; Rotondo, M; Simonetto, F; Stroili, R; Voci, C; Benayoun, M; Briand, H; Chauveau, J; David, P; de la Vaissiere, C; Del Buono, L; Hamon, O; John, M J J; Leruste, Ph; Malcles, J; Ocariz, J; Roos, L; Therin, G; Behera, P K; Gladney, L; Guo, Q H; Panetta, J; Angelini, C; Batignani, G; Bettarini, S; Bucci, F; Calderini, G; Carpinelli, M; Cenci, R; Forti, F; Giorgi, M A; Lusiani, A; Marchiori, G; Morganit, M; Neri, N; Paoloni, E; Rama, M; Rizzo, G; Walsh, J; Haire, M; Judd, D; Wagoner, D E; Biesiada, J; Danielson, N; Elmer, P; Lau, Y; Lu, C; Olsen, J; Smith, A J S; Telnov, A V; Bellini, F; Cavoto, G; D'Orazio, A; Di Marco, E; Faccini, R; Ferrarotto, F; Ferroni, F; Gaspero, M; Li Gioi, L; Mazzoni, M A; Morganti, S; Piredda, G; Polci, F; Safai Tehrani, F; Voena, C; Schröder, H; Wagner, G; Waldi, R; Adye, T; De Groot, N; Franek, B; Gopal, G P; Olaiya, E O; Wilson, F F; Purohit, M V; Weidemann, A W; Wilson, J R; Yumiceva, F X; Abe, T; Allen, M T; Aston, D; Bartoldus, R; Berger, N; Boyarski, A M; Buchmueller, O L; Claus, R; Coleman, J P; Convery, M R; Cristinziani, M; Dingfelder, J C; Dong, D; Dorfan, J; Dujmic, D; Dunwoodie, W; Fan, S; Field, R C; Glanzman, T; Gowdy, S J; Hadig, T; Halyo, V; Hast, C; Hryn'ova, T; Innes, W R; Kelsey, M H; Kim, P; Kocian, M L; Leith, D W G S; Libby, J; Luitz, S; Luth, V; Lynch, H L; Marsiske, H; Messner, R; Muller, D R; O'Grady, C P; Ozcan, V E; Perazzo, A; Perl, M; Ratcliff, B N; Roodman, A; Salnikov, A A; Schindler, R H; Schwiening, J; Snyder, A; Stelzer, J; Su, D; Sullivan, M K; Suzuki, K; Swain, S K; Thompson, J M; Va'vra, J; van Bakel, N; Weaver, M; Wisniewski, W J; Wittgen, M; Wright, D H; Yarritu, A K; Yi, K; Young, C C; Burchat, P R; Edwards, A J; Majewski, S A; Petersen, B A; Roat, C; Ahmed, M; Ahmed, S; Alam, M S; Bula, R; Ernst, J A; Saeed, M A; Wappler, F R; Zain, S B; Bugg, W; Krishnamurthy, M; Spanier, S M; Eckmann, R; Ritchie, J L; Satpathy, A; Schwitters, R F; Izen, J M; Kitayama, I; Lou, X C; Ye, S; Bianchi, F; Bona, M; Gallo, F; Gamba, D; Bomben, M; Bosisio, L; Cartaro, C; Cossutti, F; Della Ricca, G; Dittongo, S; Grancagnolo, S; Lanceri, L; Vitale, L; Panvini, R S; Banerjee, Sw; Bhuyan, B; Brown, C M; Fortin, D; Hamano, K; Kowalewski, R; Roney, J M; Sobie, R J; Back, J J; Harrison, P F; Latham, T E; Mohanty, G B; Band, H R; Chen, X; Cheng, B; Dasu, S; Datta, M; Eichenbaum, A M; Flood, K T; Graham, M; Hollar, J J; Johnson, J R; Kutter, P E; Li, H; Liu, R; Mellado, B; Mihalyi, A; Pan, Y; Prepost, R; Tan, P; von Wimmersperg-Toeller, J H; Wu, S L; Yu, Z; Neal, H; Schott, G

    2006-06-23

    We present the results of a search for the decay B0-->tau+tau- in a data sample of (232+/-3)x10(6) Upsilon(4S)-->BB decays using the BABAR detector. Certain extensions of the standard model predict measurable levels of this otherwise rare decay. We reconstruct fully one neutral B meson and seek evidence for the signal decay in the rest of the event. We find no evidence for signal events and obtain Beta(B0->tau+tau-)<4.1x10(-3) at the 90% confidence level. PMID:16907230

  14. Searches for Lepton Flavor Violation in the Decays tau+- ---> e+- gamma and tau+- ---> mu+- gamma

    SciTech Connect

    Aubert, Bernard; Karyotakis, Y.; Lees, J.P.; Poireau, V.; Prencipe, E.; Prudent, X.; Tisserand, V.; Garra Tico, J.; Grauges, E.; Martinelli, M.; Palano, A.; Pappagallo, M.; Eigen, G.; Stugu, B.; Sun, L.; Battaglia, M.; Brown, David Nathan; Hooberman, B.; Kerth, L.T.; Kolomensky, Yu.G.; Lynch, G.; /more authors..

    2010-06-11

    Searches for lepton-flavor-violating decays of a {tau} lepton to a lighter mass lepton and a photon have been performed with the entire dataset of (963 {+-} 7) x 10{sup 6} {tau} decays collected by the BABAR detector near the {Upsilon}(4S), {Upsilon}(3S) and {Upsilon}(2S) resonances. The searches yield no evidence of signals and they set upper limits on the branching fractions of {Beta}({tau}{sup {+-}} {yields} e{sup {+-}}{gamma}) < 3.3 x 10{sup -8} and {Beta}({tau}{sup {+-}} {yields} {mu}{sup {+-}}{gamma}) < 4.4 x 10{sup -8} at 90% confidence level.

  15. A Search for the Rare Decay B0 to tau+tau- atBaBar

    SciTech Connect

    Aubert, B.; Barate, R.; Boutigny, D.; Couderc, F.; Karyotakis, Y.; Lees, J.P.; Poireau, V.; Tisserand, V.; Zghiche, A.; Grauges, E.; Palano, A.; Pappagallo, M.; Pompili, A.; Chen, J.C.; Qi, N.D.; Rong, G.; Wang, P.; Zhu, Y.S.; Eigen, G.; Ofte, I.; Stugu, B. /Bergen U. /LBL, Berkeley /UC, Berkeley /Birmingham U. /Ruhr U., Bochum /Bristol U. /British Columbia U. /Brunel U. /Novosibirsk, IYF /UC, AUTHOR = Roethel, W. /UC, Irvine /UCLA /UC, Riverside /UC, San Diego /UC, Santa Barbara /UC, Santa Cruz /Caltech /Cincinnati U. /Colorado U. /Colorado State U. /DSM, DAPNIA, Saclay /Dortmund U. /Dresden, Tech. U. /Ecole Polytechnique /Edinburgh U. /Ferrara U. /INFN, Ferrara /Frascati /Genoa U. /INFN, Genoa /Harvard U. /Heidelberg U. /Valencia U., IFIC /Imperial Coll., London /Iowa U. /Iowa State U. /INFN, Perugia /Orsay, LAL /LLNL, Livermore /Liverpool U. /Queen Mary, U. of London /Royal Holloway, U. of London /Louisville U. /Manchester U. /Maryland U. /Massachusetts U., Amherst /MIT, LNS /McGill U. /Milan U. /INFN, Milan /Mississippi U. /Montreal U. /Mt. Holyoke Coll. /NIKHEF, Amsterdam /Naples U. /INFN, Naples /Notre Dame U. /Ohio State U. /Oregon U. /Padua U. /INFN, Padua /Paris U., VI-VII /Pennsylvania U. /Pisa U. /Pisa, Scuola Normale Superiore /INFN, Pisa /Prairie View A-M /Princeton U. /Rome U. /INFN, Rome /Rostock U. /Rutherford /South Carolina U. /SLAC /Stanford U., Phys. Dept. /SUNY, Albany /Tennessee U. /Texas U. /Texas U., Dallas /Turin U. /INFN, Turin /Trieste U. /INFN, Trieste /Vanderbilt U. /Victoria U. /Warwick U. /Wisconsin U., Madison /Yale U. /Karlsruhe U., EKP

    2005-11-09

    We present the results of a search for the decay B{sup 0} {yields} {tau}{sup +}{tau}{sup -} in a data sample of (232 {+-} 3) x 10{sup 6} {Upsilon}(4S) {yields} B{bar B} decays using the BABAR detector. Certain extensions of the Standard Model predict measurable levels of this otherwise rare decay. We reconstruct fully one neutral B meson and seek evidence for the signal decay in the rest of the event. We find no evidence for signal events and obtain {Beta}(B{sup 0} {yields} {tau}{sup +}{tau}{sup -}) < 3.2 x 10{sup -3} at the 90% confidence level.

  16. Progranulin reduction is associated with increased tau phosphorylation in P301L tau transgenic mice.

    PubMed

    Hosokawa, Masato; Arai, Tetsuaki; Masuda-Suzukake, Masami; Kondo, Hiromi; Matsuwaki, Takashi; Nishihara, Masugi; Hasegawa, Masato; Akiyama, Haruhiko

    2015-02-01

    Granulin (GRN) mutations have been identified in familial frontotemporal lobar degeneration patients with ubiquitin pathology. GRN transcript haploinsufficiency is proposed as a disease mechanism that leads to the loss of functional progranulin (PGRN) protein. Thus, these mutations are strongly involved in frontotemporal lobar degeneration pathogenesis. Moreover, recent findings indicate that GRN mutations are associated with other neurodegenerative disorders with tau pathology, including Alzheimer disease and corticobasal degeneration. To investigate the potential influence of a decline in PGRN protein on tau accumulation, P301L tau transgenic mice were interbred with GRN-deficient mice, producing P301L tau transgenic mice harboring the GRN hemizygote. Brains were collected from 13- and 19-month-old mice, and sequential extraction of proteins, immunoblotting, and immunohistochemical analyses were performed. Immunoblotting analysis revealed that tau phosphorylation was accelerated in the Tris-saline soluble fraction of 13-month-old and in the sarkosyl-insoluble fraction of 19-month-old P301L tau/GRN hemizygotes compared with those in fractions from P301L tau transgenic mice. Activity of cyclin-dependent kinases was also upregulated in the brains of P301L tau/GRN hemizygote mice. Although the mechanisms involved in these findings remain unknown, our data suggest that a reduction in PGRN protein might contribute to phosphorylation and intraneuronal accumulation of tau. PMID:25575133

  17. Missense tau mutations identified in FTDP-17 have a small effect on tau-microtubule interactions.

    PubMed

    DeTure, M; Ko, L W; Yen, S; Nacharaju, P; Easson, C; Lewis, J; van Slegtenhorst, M; Hutton, M; Yen, S H

    2000-01-17

    Frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17) is a group of related disorders frequently characterized by the formation of tau inclusions in neurons and glial cells. To determine whether the formation of tau inclusions in FTDP-17 results from an alteration in the ability of mutant tau to maintain the microtubule (MT) system, we compared wild type four-repeat tau with three FTDP-17 mutants (P301L, V337M and R406W) for their ability to bind MT, promote MT assembly and bundling. According to in vitro binding and assembly assays, P301L is the only mutant that demonstrates a small, yet significant reduction, in its affinity for MT while both P301L and R406W have a small reduction in their ability to promote tubulin assembly. Based on studies of neuroblastoma and CHO cells transfected with GFP-tagged tau DNA constructs, both mutant and wild type tau transfectants were indistinguishable in the distribution pattern of tau in terms of co-localization with MT and generation of MT bundles. These results suggest that missense mutation of tau gene do not have an immediate impact on the integrity of MT system, and that exposure of affected neurons to additional insults or factors (e.g., aging) may be needed to initiate the formation of tau inclusions in FTDP-17. PMID:10627302

  18. Orbital motions and light curves of young binaries XZ Tau and VY Tau

    NASA Astrophysics Data System (ADS)

    Dodin, A. V.; Emelyanov, N. V.; Zharova, A. V.; Lamzin, S. A.; Malogolovets, E. V.; Roe, J. M.

    2016-01-01

    The results of our speckle interferometric observations of young binaries VY Tau and XZ Tau are presented. For the first time, we found a relative displacement of VY Tau components as well as a preliminary orbit for XZ Tau. It appeared that the orbit is appreciably non-circular and is inclined by i ≲ 47◦ from the plane of the sky. It means that the rotation axis of XZ Tau A and the axis of its jet are significantly non-perpendicular to the orbital plane. We found that the average brightness of XZ Tau had been increasing from the beginning of the last century up to the mid-thirties and then it decreased by Δ B > 2 mag. The maximal brightness has been reached significantly later on the time of periastron passage. The total brightness of XZ Tau's components varied in a non-regular way from 1970 to 1985 when eruptions of hot gas from XZ Tau A presumably had occurred. In the early nineties the variations became regular following which a chaotic variability had renewed. We also report that a flare activity of VY Tau has resumed after 40 yr pause, parameters of the previous and new flares are similar, and the flares are related with the A component.

  19. Park2-null/tau transgenic mice reveal a functional relationship between parkin and tau.

    PubMed

    Guerrero, Rosa; Navarro, Paloma; Gallego, Eva; Avila, Jesus; de Yebenes, Justo G; Sanchez, Marina P

    2008-03-01

    Mutations, haplotypes, and polymorphisms of tau and Park-2 genes constitute risk factors for developing tauopathies. In order to analyze the possible relationship between parkin and tau we generated a double-mutant mouse deficient for Park-2 expression and overexpressing a mutant tau protein (hTauVLW). Mice develop normally, although the median survival rate is considerably reduced with respect to wild type (45%). Aggregates of phosphorylated tau in neurons and reactive gliosis are quite abundant in cortex and hippocampus of these mice. Moreover, while in young transgenic mice the hTauVLW immunostained transgene product is observed in both cell bodies and dendrites, the hTauVLW mutant protein is only detected in the neuronal cell bodies when Park-2 gene is additionally deleted. Moreover, DNA fragmentation was detected by the TUNEL method, and cerebral atrophy is also present in these regions. The levels of phosphorylated tau and Hsp70 are increased in the double-mutant mice, while CHIP expression in hippocampus is lower when the Park-2 gene is deleted. Thus, the combination of Park-2 gene deletion with hTauVLW transgene overexpression in mice produces serious neuropathological effects, which reflect the existence of some relationship between both proteins. PMID:18376058

  20. Tau longitudinal polarization in B{yields}D{tau}{nu} and its role in the search for the charged Higgs boson

    SciTech Connect

    Tanaka, Minoru; Watanabe, Ryoutaro

    2010-08-01

    We study the longitudinal polarization of the tau lepton in B{yields}D{tau}{nu} decay. After discussing possible sensitivities of {tau} decay modes to the {tau} polarization, we examine the effect of charged Higgs boson on the {tau} polarization in B{yields}D{tau}{nu}. We find a relation between the decay rate and the {tau} polarization, and clarify the role of the {tau} polarization measurement in the search for the charged Higgs boson.

  1. Deletion of endogenous Tau proteins is not detrimental in Drosophila.

    PubMed

    Burnouf, Sylvie; Grönke, Sebastian; Augustin, Hrvoje; Dols, Jacqueline; Gorsky, Marianna Karina; Werner, Jennifer; Kerr, Fiona; Alic, Nazif; Martinez, Pedro; Partridge, Linda

    2016-01-01

    Human Tau (hTau) is a highly soluble and natively unfolded protein that binds to microtubules within neurons. Its dysfunction and aggregation into insoluble paired helical filaments is involved in the pathogenesis of Alzheimer's disease (AD), constituting, together with accumulated β-amyloid (Aβ) peptides, a hallmark of the disease. Deciphering both the loss-of-function and toxic gain-of-function of hTau proteins is crucial to further understand the mechanisms leading to neurodegeneration in AD. As the fruit fly Drosophila melanogaster expresses Tau proteins (dTau) that are homologous to hTau, we aimed to better comprehend dTau functions by generating a specific tau knock-out (KO) fly line using homologous recombination. We observed that the specific removal of endogenous dTau proteins did not lead to overt, macroscopic phenotypes in flies. Indeed, survival, climbing ability and neuronal function were unchanged in tau KO flies. In addition, we did not find any overt positive or negative effect of dTau removal on human Aβ-induced toxicity. Altogether, our results indicate that the absence of dTau proteins has no major functional impact on flies, and suggests that our tau KO strain is a relevant model to further investigate the role of dTau proteins in vivo, thereby giving additional insights into hTau functions. PMID:26976084

  2. Deletion of endogenous Tau proteins is not detrimental in Drosophila

    PubMed Central

    Burnouf, Sylvie; Grönke, Sebastian; Augustin, Hrvoje; Dols, Jacqueline; Gorsky, Marianna Karina; Werner, Jennifer; Kerr, Fiona; Alic, Nazif; Martinez, Pedro; Partridge, Linda

    2016-01-01

    Human Tau (hTau) is a highly soluble and natively unfolded protein that binds to microtubules within neurons. Its dysfunction and aggregation into insoluble paired helical filaments is involved in the pathogenesis of Alzheimer’s disease (AD), constituting, together with accumulated β-amyloid (Aβ) peptides, a hallmark of the disease. Deciphering both the loss-of-function and toxic gain-of-function of hTau proteins is crucial to further understand the mechanisms leading to neurodegeneration in AD. As the fruit fly Drosophila melanogaster expresses Tau proteins (dTau) that are homologous to hTau, we aimed to better comprehend dTau functions by generating a specific tau knock-out (KO) fly line using homologous recombination. We observed that the specific removal of endogenous dTau proteins did not lead to overt, macroscopic phenotypes in flies. Indeed, survival, climbing ability and neuronal function were unchanged in tau KO flies. In addition, we did not find any overt positive or negative effect of dTau removal on human Aβ-induced toxicity. Altogether, our results indicate that the absence of dTau proteins has no major functional impact on flies, and suggests that our tau KO strain is a relevant model to further investigate the role of dTau proteins in vivo, thereby giving additional insights into hTau functions. PMID:26976084

  3. The winds from HL Tau

    NASA Astrophysics Data System (ADS)

    Klaassen, P. D.; Mottram, J. C.; Maud, L. T.; Juhasz, A.

    2016-07-01

    Outflowing motions, whether a wind launched from the disc, a jet launched from the protostar, or the entrained molecular outflow, appear to be a ubiquitous feature of star formation. These outwards motions have a number of root causes, and how they manifest is intricately linked to their environment as well as the process of star formation itself. Using the Atacama Large Millimeter/submillimeter Array (ALMA) Science Verification data of HL Tau, we investigate the high-velocity molecular gas being removed from the system as a result of the star formation process. We aim to place these motions in context with the optically detected jet, and the disc. With these high-resolution (˜1 arcsec) ALMA observations of CO (J=1-0), we quantify the outwards motions of the molecular gas. We find evidence for a bipolar outwards flow, with an opening angle, as measured in the redshifted lobe, starting off at 90°, and narrowing to 60° further from the disc, likely because of magnetic collimation. Its outwards velocity, corrected for inclination angle is of the order of 2.4 km s-1.

  4. The winds from HL Tau

    PubMed Central

    Klaassen, P. D.; Mottram, J. C.; Maud, L. T.; Juhasz, A.

    2016-01-01

    Outflowing motions, whether a wind launched from the disc, a jet launched from the protostar, or the entrained molecular outflow, appear to be a ubiquitous feature of star formation. These outwards motions have a number of root causes, and how they manifest is intricately linked to their environment as well as the process of star formation itself. Using the Atacama Large Millimeter/submillimeter Array (ALMA) Science Verification data of HL Tau, we investigate the high-velocity molecular gas being removed from the system as a result of the star formation process. We aim to place these motions in context with the optically detected jet, and the disc. With these high-resolution (∼1 arcsec) ALMA observations of CO (J=1−0), we quantify the outwards motions of the molecular gas. We find evidence for a bipolar outwards flow, with an opening angle, as measured in the redshifted lobe, starting off at 90°, and narrowing to 60° further from the disc, likely because of magnetic collimation. Its outwards velocity, corrected for inclination angle is of the order of 2.4 km s−1. PMID:27559304

  5. The winds from HL Tau

    NASA Astrophysics Data System (ADS)

    Klaassen, P. D.; Mottram, J. C.; Maud, L. T.; Juhasz, A.

    2016-04-01

    Outflowing motions, whether a wind launched from the disk, a jet launched from the protostar, or the entrained molecular outflow, appear to be an ubiquitous feature of star formation. These outwards motions have a number of root causes, and how they manifest is intricately linked to their environment as well as the process of star formation itself. Using the ALMA Science Verification data of HL Tau, we investigate the high velocity molecular gas being removed from the system as a result of the star formation process. We aim to place these motions in context with the optically detected jet, and the disk. With these high resolution (˜1″) ALMA observations of CO (J=1-0), we quantify the outwards motions of the molecular gas. We find evidence for a bipolar outwards flow, with an opening angle, as measured in the red-shifted lobe, starting off at 90°, and narrowing to 60° further from the disk, likely because of magnetic collimation. Its outwards velocity, corrected for inclination angle is of order 2.4 km s-1.

  6. Common Core Literacy Lesson Plans: Ready-to-Use Resources, K-5

    ERIC Educational Resources Information Center

    Davis, Lauren

    2013-01-01

    Schools nationwide are transitioning to the Common Core--our advice to you: Don't go it alone! Our new book, "Common Core Literacy Lesson Plans: Ready-to-Use Resources, K-5," shows you that teaching the Common Core State Standards in the elementary grades doesn't have to be intimidating! This easy-to-use guide provides model lesson plans for…

  7. Escherichia coli K5 capsule expression enhances colonization of the large intestine in the gnotobiotic rat.

    PubMed Central

    Hérias, M V; Midtvedt, T; Hanson, L A; Wold, A E

    1997-01-01

    The role of capsule expression in the capacity of Escherichia coli to colonize in the large intestinal environment was studied in a gnotobiotic rat model. The rats were given perorally a mixture of two mutant strains differing in K5 expression. After 2 weeks, the rats were sacrificed, and subsequently intestinal contents, intestinal mucosae, and mesenteric lymph nodes were homogenized and bacterial numbers were quantified. Two E. coli mutant pairs were used, the first pair (972-998) lacking the O-specific side chain and the second pair (973-997) carrying the O75 lipopolysaccharide. The K5+ mutants established themselves at a higher level than the K5- mutants (10(9) versus 10(6) CFU/g [P < 0.001] for the first pair and 10(9) versus 10(8) CFU/g [P < 0.01] for the second pair, respectively). The results were confirmed by serology showing a K5+ phenotype for practically all isolates. The bacterial population associated with the mucosa was similar to that in the luminal contents with respect to the proportions of the respective mutants, and translocation occurred in numbers proportional to the intestinal population densities of the respective mutants. All mutants were able to express type 1 as well as P fimbriae. After colonization, the expression of P fimbriae remained high whereas only a minority of the isolates expressed type 1 fimbriae. The results suggest that capsule expression and P fimbriae enhance intestinal colonization by E. coli and that these virulence factors, by increasing bacterial densities in the intestine, secondarily increase translocation. PMID:9009309

  8. The decay. tau. sup minus r arrow K sup minus K sup +. pi. sup minus. nu. sub. tau. and the. nu. sub. tau. mass

    SciTech Connect

    Gomez-Cadenas, J.J. ); Gonzalez-Garcia, M.C.; Pich, A. Instituto de Fisica Corpuscular, Consejo Superior de Investigaciones Cientificas, Universidad de Valencia, Burjasot )

    1990-11-01

    In this paper, we present a model based on the effective chiral Lagrangian to describe the decay {tau}{sup {minus}}{r arrow}{ital K}{sup {minus}}{ital K}{sup +}{pi}{sup {minus}}{nu}{sub {tau}}. Using our model we study the possible limits on the {nu}{sub {tau}} mass that can be achieved by a high-statistics, high-precision experiment taking data close to the {tau}-pair production threshold.

  9. The future of tau physics and tau-charm detector and factory design

    SciTech Connect

    Perl, M.L.

    1991-02-01

    Future research on the tau lepton requires large statistics, thorough investigation of systematic errors, and direct experimental knowledge of backgrounds. Only a tau-charm factory with a specially designed detector can provide all the experimental conditions to meet these requirements. This paper is a summary of three lectures delivered at the 1991 Lake Louise Winter Institute.

  10. Protoplanetary disk formation and evolution models: DM Tau and GM Aur

    NASA Astrophysics Data System (ADS)

    Hueso, R.; Guillot, T.

    2002-09-01

    We study the formation and evolution of protoplanetary disks using an axisymmetric turbulent disk model. We compare model results with observational parameters derived for the DM Tau and GM Aur systems. These are relatively old T Tauri stars with large and massive protoplanetary disks. Early disk formation is studied in the standard scenario of slowly rotating isothermal collapsing spheres and is strongly dependent on the initial angular momentum and the collapse accretion rate. The viscous evolution of the disk is integrated in time using the classical Alpha prescription of turbulence. We follow the temporal evolution of the disks until their characteristics fit the observed characteristics of DM Tau and GM Aur. We therefore obtain the set of model parameters that are able to explain the present state of these disks. We also study the disk evolution under the Beta parameterization of turbulence, recently proposed for sheared flows on protoplanetary disks. Both parameterizations allow explaining the present state of both DM Tau and GM Aur. We infer a value of Alpha between 5x10-3 to 0.02 for DM Tau and one order of magnitude smaller for GM Aur. Values of the Beta parameter are in accordance with theoretical predictions of Beta around 2x10-5 but with a larger dispersion on other model parameters, which make us favor the Alpha parameterization of turbulence. Implications for planetary system development in these systems are presented. In particular, GM Aur is a massive and slowly evolving disk where conditions are very favorable for planetesimal growth. The large value of present disk mass and the relatively small observed accretion rate of this system may also be indicative of the presence of an inner gas giant planet. Acknowledgements: This work has been supported by Programme Nationale de Planetologie. R. Hueso acknowledges a post-doctoral fellowship from Gobierno Vasco.

  11. Study of the Tau- to Pi- Pi+ Pi- Pi0 Nu/Tau And Tau- to Pi- Pi- Pi+ Eta Nu/Tau Decays Using the BaBar Detector

    SciTech Connect

    Sobie, Randall; /Victoria U.

    2007-11-14

    The {tau}{sup -} {yields} {pi}{sup -}{pi}{sup +}{pi}{sup -}{nu}{sub {tau}} and {tau}{sup -} {yields} {pi}{sup -}{pi}{sup -}{pi}{sup +}{eta}{nu}{sub {tau}} decays have been studied with the BABAR detector. Preliminary branching fractions on the two modes are presented. The {tau}{sup -} {yields} {pi}{sup -}{pi}{sup -}{pi}{sup +}{eta}{nu}{sub {tau}} mode is found to have a large contribution from the {tau}{sup -} {yields} {omega}{pi}{sup -}{nu}{sub {tau}} decay. The {tau}{sup -} {yields} {pi}{sup -}{pi}{sup -}{pi}{sup +}{eta}{nu}{sub {tau}} decay is studied using the {eta} {yields} {gamma}{gamma} mode and the {tau}{sup -} f{sub 1}(1285){pi}{sup -}{nu}{sub {tau}} decay is seen to be the primary source of these decays. A 90% confidence level upper limit is placed on the {tau}{sup -} {yields} {eta}{prime}(958){pi}{sup -}{nu}{sub {tau}} decay which proceeds through a second-class current and is expected to be forbidden in the limit of perfect isospin symmetry.

  12. Curcumin improves tau-induced neuronal dysfunction of nematodes.

    PubMed

    Miyasaka, Tomohiro; Xie, Ce; Yoshimura, Satomi; Shinzaki, Yuki; Yoshina, Sawako; Kage-Nakadai, Eriko; Mitani, Shohei; Ihara, Yasuo

    2016-03-01

    Tau is a key protein in the pathogenesis of various neurodegenerative diseases, which are categorized as tauopathies. Because the extent of tau pathologies is closely linked to that of neuronal loss and the clinical symptoms in Alzheimer's disease, anti-tau therapeutics, if any, could be beneficial to a broad spectrum of tauopathies. To learn more about tauopathy, we developed a novel transgenic nematode (Caenorhabditis elegans) model that expresses either wild-type or R406W tau in all the neurons. The wild-type tau-expressing worms exhibited uncoordinated movement (Unc) and neuritic abnormalities. Tau accumulated in abnormal neurites that lost microtubules. Similar abnormalities were found in the worms that expressed low levels of R406W-tau but were not in those expressing comparative levels of wild-type tau. Biochemical studies revealed that tau is aberrantly phosphorylated but forms no detergent-insoluble aggregates. Drug screening performed in these worms identified curcumin, a major phytochemical compound in turmeric, as a compound that reduces not only Unc but also the neuritic abnormalities in both wild-type and R406W tau-expressing worms. Our observations suggest that microtubule stabilization mediates the antitoxicity effect of curcumin. Curcumin is also effective in the worms expressing tau fragment, although it does not prevent the formation of tau-fragment dimers. These data indicate that curcumin improves the tau-induced neuronal dysfunction that is independent of insoluble aggregates of tau. PMID:26923403

  13. Alpha Particle

    NASA Astrophysics Data System (ADS)

    Murdin, P.

    2000-11-01

    Term that is sometimes used to describe a helium nucleus, a positively charged particle that consists of two protons and two neutrons, bound together. Alpha particles, which were discovered by Ernest Rutherford (1871-1937) in 1898, are emitted by atomic nuclei that are undergoing alpha radioactivity. During this process, an unstable heavy nucleus spontaneously emits an alpha particle and transmut...

  14. Simulated Cytoskeletal Collapse via Tau Degradation

    PubMed Central

    Sendek, Austin; Fuller, Henry R.; Hayre, N. Robert; Singh, Rajiv R. P.; Cox, Daniel L.

    2014-01-01

    We present a coarse-grained two dimensional mechanical model for the microtubule-tau bundles in neuronal axons in which we remove taus, as can happen in various neurodegenerative conditions such as Alzheimers disease, tauopathies, and chronic traumatic encephalopathy. Our simplified model includes (i) taus modeled as entropic springs between microtubules, (ii) removal of taus from the bundles due to phosphorylation, and (iii) a possible depletion force between microtubules due to these dissociated phosphorylated taus. We equilibrate upon tau removal using steepest descent relaxation. In the absence of the depletion force, the transverse rigidity to radial compression of the bundles falls to zero at about 60% tau occupancy, in agreement with standard percolation theory results. However, with the attractive depletion force, spring removal leads to a first order collapse of the bundles over a wide range of tau occupancies for physiologically realizable conditions. While our simplest calculations assume a constant concentration of microtubule intercalants to mediate the depletion force, including a dependence that is linear in the detached taus yields the same collapse. Applying percolation theory to removal of taus at microtubule tips, which are likely to be the protective sites against dynamic instability, we argue that the microtubule instability can only obtain at low tau occupancy, from 0.06–0.30 depending upon the tau coordination at the microtubule tips. Hence, the collapse we discover is likely to be more robust over a wide range of tau occupancies than the dynamic instability. We suggest in vitro tests of our predicted collapse. PMID:25162587

  15. Inhibition of Both Hsp70 Activity and Tau Aggregation in Vitro Best Predicts Tau Lowering Activity of Small Molecules.

    PubMed

    Martin, Mackenzie D; Baker, Jeremy D; Suntharalingam, Amirthaa; Nordhues, Bryce A; Shelton, Lindsey B; Zheng, Dali; Sabbagh, Jonathan J; Haystead, Timothy A J; Gestwicki, Jason E; Dickey, Chad A

    2016-07-15

    Three scaffolds with inhibitory activity against the heat shock protein 70 (Hsp70) family of chaperones have been found to enhance the degradation of the microtubule associated protein tau in cells, neurons, and brain tissue. This is important because tau accumulation is linked to neurodegenerative diseases including Alzheimer's disease (AD) and chronic traumatic encephalopathy (CTE). Here, we expanded upon this study to investigate the anti-tau efficacy of additional scaffolds with Hsp70 inhibitory activity. Five of the nine scaffolds tested lowered tau levels, with the rhodacyanine and phenothiazine scaffolds exhibiting the highest potency as previously described. Because phenothiazines also inhibit tau aggregation in vitro, we suspected that this activity might be a more accurate predictor of tau lowering. Interestingly, the rhodacyanines did inhibit in vitro tau aggregation to a similar degree as phenothiazines, correlating well with tau-lowering efficacy in cells and ex vivo slices. Moreover, other Hsp70 inhibitor scaffolds with weaker tau-lowering activity in cells inhibited tau aggregation in vitro, albeit at lower potencies. When we tested six well-characterized tau aggregation inhibitors, we determined that this mechanism of action was not a better predictor of tau-lowering than Hsp70 inhibition. Instead, we found that compounds possessing both activities were the most effective at promoting tau clearance. Moreover, cytotoxicity and PAINS activity are critical factors that can lead to false-positive lead identification. Strategies designed around these principles will likely yield more efficacious tau-lowering compounds. PMID:27177119

  16. Tau neutrino component to tritium beta decay

    SciTech Connect

    Snyderman, N.J.

    1995-06-01

    A framework is given for explaining anomalous results of neutrino mass experiments that measure the high energy electron spectrum of tritium {beta} decay. The experimental results have been fit to a negative neutrino mass square. We show that there is a consistent phenomenological interpretation due to a positive mass tau neutrino component of the {beta} decay spectrum, with strong near threshold final state interactions with the He nucleus. If this enhancement is due to new interactions between low energy tau neutrinos and nuclei, then the tritium 0 decay experiments could be used as detectors for cosmic background tau neutrinos. The model predicts a distinctive spectrum shape that is consistent with a recent high statistics LLNL experiment. A fit to the experiment gives a tau neutrino mass of 23 eV. Tau neutrinos of this mass would dominate the mass of the universe. Requirements for a theoretical model are given, as well as models that realize different aspects of these requirements. While qualitatively successful, the theoretical models have such severe quantitative difficulties that the accuracy of the molecular physics of the T-{sup 3}He ion, assumed in the analysis of the experimental data, is called into question.

  17. Targeted deletion of Atg5 reveals differential roles of autophagy in keratin K5-expressing epithelia

    SciTech Connect

    Sukseree, Supawadee; Rossiter, Heidemarie; Mildner, Michael; Pammer, Johannes; Buchberger, Maria; Gruber, Florian; Watanapokasin, Ramida; Tschachler, Erwin; Eckhart, Leopold

    2013-01-11

    Highlights: Black-Right-Pointing-Pointer We generated mice lacking Atg5 and autophagy in keratin K5-positive epithelia. Black-Right-Pointing-Pointer Suppression of autophagy in thymic epithelium was not associated with signs of autoimmunity. Black-Right-Pointing-Pointer Autophagy was required for normal terminal differentiation of preputial gland cells. Black-Right-Pointing-Pointer Autophagy-deficient cells of the preputial glands degraded nuclear DNA prematurely. -- Abstract: Autophagy contributes to the homeostasis of many tissues, yet its role in epithelia is incompletely understood. A recent report proposed that Atg5-dependent autophagy in thymic epithelial cells is essential for their function in the negative selection of self-reactive T-cells and, thus, for the suppression of tissue inflammation. Here we crossed mice carrying floxed alleles of the Atg5 gene with mice expressing the Cre recombinase under the control of the keratin K5 promoter to suppress autophagy in all K5-positive epithelia. The efficiency of autophagy abrogation was confirmed by immunoanalyses of LC3, which was converted to the autophagy-associated LC3-II form in normal but not Atg5-deficient cells, and of p62, which accumulated in Atg5-deficient cells. Mice carrying the epithelium-specific deletion of Atg5 showed normal weight gain, absence of tissue inflammation, and a normal morphology of the thymic epithelium. By contrast, autophagy-deficient epithelial cells of the preputial gland showed aberrant eosinophilic staining in histology and premature degradation of nuclear DNA during terminal differentiation. Taken together, the results of this study suggest that autophagy is dispensable for the suppression of autoimmunity by thymic epithelial cells but essential for normal differentiation of the preputial gland in mice.

  18. Study of the tau- ---> pi- pi- pi+ pi0 pi0 nu/tau and tau- --> 3h- 2h+ nu/tau Decays Using the BaBar Detector

    SciTech Connect

    Sobie, R.; /Victoria U.

    2005-06-21

    The {tau}{sup -} {yields} {pi}{sup -}{pi}{sup -}{pi}{sup +}{pi}{sup 0}{pi}{sup 0}{nu}{sub {tau}} and {tau}{sup -} {yields} 3h{sup -} 2h{sup +} {nu}{sub {tau}} decays have been studied using the BABAR experiment at the PEP-II e{sup +}e{sup -} storage ring. Preliminary branching fractions are given for the {tau}{sup -} {yields} {pi}{sup -}{pi}{sup -}{pi}{sup +}{pi}{sup 0}{pi}{sup 0}{nu}{sub {tau}} and to the sub-channels {tau}{sup -} {yields} {eta}{pi}{sup -} {pi}{sup 0}{nu}{sub {tau}} and {tau}{sup -} {yields} {omega}(782){pi}{sup -}{pi}{sup 0}{nu}{sub {tau}}. A preliminary upper limit is given on the branching fraction for the {phi}(1020){pi}{sup -}{pi}{sup 0}{nu}{sub {tau}} mode. In addition a preliminary measurement of the branching fraction of the {tau}{sup -} {yields} 3h{sup -}2h{sup +} {nu}{sub {tau}} decay (h = {pi}, K) is presented.

  19. Pathological tau disrupts ongoing network activity.

    PubMed

    Menkes-Caspi, Noa; Yamin, Hagar G; Kellner, Vered; Spires-Jones, Tara L; Cohen, Dana; Stern, Edward A

    2015-03-01

    Pathological tau leads to dementia and neurodegeneration in tauopathies, including Alzheimer's disease. It has been shown to disrupt cellular and synaptic functions, yet its effects on the function of the intact neocortical network remain unknown. Using in vivo intracellular and extracellular recordings, we measured ongoing activity of neocortical pyramidal cells during various arousal states in the rTg4510 mouse model of tauopathy, prior to significant cell death, when only a fraction of the neurons show pathological tau. In transgenic mice, membrane potential oscillations are slower during slow-wave sleep and under anesthesia. Intracellular recordings revealed that these changes are due to longer Down states and state transitions of membrane potentials. Firing rates of transgenic neurons are reduced, and firing patterns within Up states are altered, with longer latencies and inter-spike intervals. By changing the activity patterns of a subpopulation of affected neurons, pathological tau reduces the activity of the neocortical network. PMID:25704951

  20. PICALM modulates autophagy activity and tau accumulation

    PubMed Central

    Moreau, Kevin; Fleming, Angeleen; Imarisio, Sara; Lopez Ramirez, Ana; Mercer, Jacob L.; Jimenez-Sanchez, Maria; Bento, Carla F.; Puri, Claudia; Zavodszky, Eszter; Siddiqi, Farah; Lavau, Catherine P.; Betton, Maureen; O’Kane, Cahir J.; Wechsler, Daniel S.; Rubinsztein, David C.

    2014-01-01

    Genome-wide association studies have identified several loci associated with Alzheimer’s disease (AD), including proteins involved in endocytic trafficking such as PICALM/CALM (phosphatidylinositol binding clathrin assembly protein). It is unclear how these loci may contribute to AD pathology. Here we show that CALM modulates autophagy and alters clearance of tau, a protein which is a known autophagy substrate and which is causatively linked to AD, both in vitro and in vivo. Furthermore, altered CALM expression exacerbates tau-mediated toxicity in zebrafish transgenic models. CALM influences autophagy by regulating the endocytosis of SNAREs, such as VAMP2, VAMP3 and VAMP8, which have diverse effects on different stages of the autophagy pathway, from autophagosome formation to autophagosome degradation. This study suggests that the AD genetic risk factor CALM modulates autophagy, and this may affect disease in a number of ways including modulation of tau turnover. PMID:25241929

  1. The Tau Lepton and the Search for New Elementary Particle Physics

    SciTech Connect

    Perl, Martin L.

    1998-11-18

    This Fifth International WEIN Symposium is devoted to physics beyond the standard model. This talk is about tau lepton physics, but I begin with the question: do we know how to find new physics in the world of elementary particles? This question is interwoven with the various tau physics topics. These topics are: searching for unexpected tau decay modes; searching for additional tau decay mechanisms; radiative tau decays; tau decay modes of the W, B, and D; decay of the Z{sup 0} to tau pairs; searching for CP violation in tau decay; the tau neutrino, dreams and odd ideas in tau physics; and tau research facilities in the next decades.

  2. Microtubule-associated protein tau in bovine retinal photoreceptor rod outer segments: comparison with brain tau.

    PubMed

    Yamazaki, Akio; Nishizawa, Yuji; Matsuura, Isao; Hayashi, Fumio; Usukura, Jiro; Bondarenko, Vladimir A

    2013-10-01

    Recent studies have suggested a possible involvement of abnormal tau in some retinal degenerative diseases. The common view in these studies is that these retinal diseases share the mechanism of tau-mediated degenerative diseases in brain and that information about these brain diseases may be directly applied to explain these retinal diseases. Here we collectively examine this view by revealing three basic characteristics of tau in the rod outer segment (ROS) of bovine retinal photoreceptors, i.e., its isoforms, its phosphorylation mode and its interaction with microtubules, and by comparing them with those of brain tau. We find that ROS contains at least four isoforms: three are identical to those in brain and one is unique in ROS. All ROS isoforms, like brain isoforms, are modified with multiple phosphate molecules; however, ROS isoforms show their own specific phosphorylation pattern, and these phosphorylation patterns appear not to be identical to those of brain tau. Interestingly, some ROS isoforms, under the normal conditions, are phosphorylated at the sites identical to those in Alzheimer's patient isoforms. Surprisingly, a large portion of ROS isoforms tightly associates with a membranous component(s) other than microtubules, and this association is independent of their phosphorylation states. These observations strongly suggest that tau plays various roles in ROS and that some of these functions may not be comparable to those of brain tau. We believe that knowledge about tau in the entire retinal network and/or its individual cells are also essential for elucidation of tau-mediated retinal diseases, if any. PMID:23712071

  3. Probing keratinocyte and differentiation specificity of the human K5 promoter in vitro and in transgenic mice.

    PubMed Central

    Byrne, C; Fuchs, E

    1993-01-01

    Keratins K5 and K14 form the extensive intermediate filament network of mitotically active basal cells in all stratified epithelia. We have explored the regulatory mechanisms governing cell-type-specific and differentiation stage-specific expression of the human K5 gene in transiently transfected keratinocytes in vitro and in transgenic mice in vivo. Six thousand base pairs of 5' upstream K5 sequence directed proper basal cell-specific expression in all stratified epithelia. Surprisingly, as few as 90 bp of the K5 promoter still directed expression to stratified epithelia, with expression predominantly in epidermis, hair follicles, and tongue. Despite keratinocyte-preferred expression, the truncated K5 promoter displayed departures from basal to suprabasal expression in epidermis and from outer root sheath to inner root sheath expression in the follicle, with some regional variations in expression as well. To begin to elucidate the molecular controls underlying the keratinocyte specificity of the truncated promoter, we examined protein-DNA interactions within this region. A number of keratinocyte nuclear proteins bind to a K5 gene segment extending from -90 to +32 bp and are functionally involved in transcriptional regulation in vitro. Interestingly, several of these factors are common to both the K5 and K14 promoters, although they appear to be distinct from those previously implicated in keratinocyte specificity. Mutagenesis studies indicate that factors binding in the vicinity of the TATA box and transcription initiation are responsible for the cell type specificity of the truncated K5 promoter. Images PMID:7684490

  4. Can we see tau-Flavour Violation at the LHC?

    SciTech Connect

    Carquin, E.; Gomez, M. E.; Rodriguez-Quintero, J.

    2010-02-10

    We study the conditions required for chi{sub 2}->chi+tau{sup +}-mu{sup +}- decays to yield observable tau flavour violation at the LHC, for cosmologically interesting values of the neutralino relic density.

  5. Tau physics at p[bar p] colliders

    SciTech Connect

    Konigsberg, J. . High Energy Physics Lab.)

    1993-01-01

    Tau detection techniques in hadron colliders are discussed together with the measurements and searches performed so far. We also underline the importance tau physics has in present and future collider experiments.

  6. Tau physics at p{bar p} colliders

    SciTech Connect

    Konigsberg, J.

    1993-01-01

    Tau detection techniques in hadron colliders are discussed together with the measurements and searches performed so far. We also underline the importance tau physics has in present and future collider experiments.

  7. Tau phosphorylation at Alzheimer's disease-related Ser356 contributes to tau stabilization when PAR-1/MARK activity is elevated.

    PubMed

    Ando, Kanae; Oka, Mikiko; Ohtake, Yosuke; Hayashishita, Motoki; Shimizu, Sawako; Hisanaga, Shin-Ichi; Iijima, Koichi M

    2016-09-16

    Abnormal phosphorylation of the microtubule-associated protein tau is observed in many neurodegenerative diseases, including Alzheimer's disease (AD). AD-related phosphorylation of two tau residues, Ser262 and Ser356, by PAR-1/MARK stabilizes tau in the initial phase of mismetabolism, leading to subsequent phosphorylation events, accumulation, and toxicity. However, the relative contribution of phosphorylation at each of these sites to tau stabilization has not yet been elucidated. In a Drosophila model of human tau toxicity, we found that tau was phosphorylated at Ser262, but not at Ser356, and that blocking Ser262 phosphorylation decreased total tau levels. By contrast, when PAR-1 was co-overexpressed with tau, tau was hyperphosphorylated at both Ser262 and Ser356. Under these conditions, the protein levels of tau were significantly elevated, and prevention of tau phosphorylation at both residues was necessary to completely suppress this elevation. These results suggest that tau phosphorylation at Ser262 plays the predominant role in tau stabilization when PAR-1/MARK activity is normal, whereas Ser356 phosphorylation begins to contribute to this process when PAR-1/MARK activity is abnormally elevated, as in diseased brains. PMID:27520376

  8. Multiple-neutral-meson decays of the /tau/ lepton and electromagnetic calorimeter requirements at Tau-Charm Factory

    SciTech Connect

    Gan, K.K.

    1989-08-01

    This is a study of the physics sensitivity to the multiple-neutral-meson decays of the /tau/ lepton at the Tau-Charm Factory. The sensitivity is compared for a moderate and an ultimate electromagnetic calorimeter. With the high luminosity of the Tau- Charm Factory, a very large sample of the decays /tau//sup /minus// /yields/ /pi//sup /minus//2/pi//sup 0//nu//sub /tau// and /tau//sup /minus// /yields/ /pi//sup /minus//3/pi//sup 0//nu//sub /tau// can be collected with both detectors. However, with the ultimate detector, 2/pi//sup 0/ and 3/pi//sup 0/ can be unambiguously reconstructed with very little background. For the suppressed decay /tau//sup /minus// /yields/ /pi//sup /minus///eta//pi//sup 0//nu//sub /tau//, only the ultimate detector has the sensitivity. The ultimate detector is also sensitive to the more suppressed decay /tau//sup /minus// /yields/ K/sup /minus///eta//nu//sub /tau// and the moderate detector may have the sensitivity if the hadronic background is not significantly larger than that predicted by Lund. In the case of the highly suppressed second-class-current decay /tau//sup /minus// /yields/ /pi//sup /minus///eta//nu//sub /tau//, only the ultimate detector has sensitivity. The sensitivity can be greatly enhanced with a small-angle photon veto. 16 refs., 9 figs., 2 tabs.

  9. Search for Second-Class Currents in tau- -> omega.pi-.nu_tau

    SciTech Connect

    Aubert, B.

    2009-04-22

    We report an analysis of {tau}{sup -} decaying into {omega}{pi}{sup -} {nu}{sub {tau}} with {omega} {yields} {pi}{sup +}{pi}{sup -}{pi}{sup 0} using a data sample containing nearly 320 million {tau} pairs collected with the BABAR detector at the PEP-II B-Factory. We find no evidence for second-class currents and we set an upper limit of 0.69% at 90% confidence level for the fraction of second-class currents in this decay mode.

  10. Elimination of spurious eigenvalues in the Chebyshev tau spectral method

    NASA Technical Reports Server (NTRS)

    Mcfadden, G. B.; Murray, B. T.; Boisvert, R. F.

    1990-01-01

    A very simple modification is presented for the Chebyshev tau method which can eliminate spurious eigenvalues, proceeding from a consideration of the vorticity-streamfunction reformulation of the Chebyshev tau method and the Chebyshev-Galerkin method, which have no spurious modes. Consideration of a model problem indicates that these two approaches are equivalent, and that they reduce to the present modification of the tau method. This modified tau method also eliminates spurious eigenvalues from the Orr-Sommerfeld equation.

  11. Microglial tau undergoes phosphorylation-independent modification after ischemia.

    PubMed

    Uchihara, Toshiki; Nakamura, Ayako; Arai, Tetsuaki; Ikeda, Kenji; Tsuchiya, Kuniaki

    2004-01-15

    Tau2 is a phosphorylation-independent antibody that immunolabels neurofibrillary tangles (NFTs) of Alzheimer type and microglia around ischemic foci on formalin-fixed, paraffin-embedded sections. We found that copresence of polyethyleneglycol-p-isooctylphenyl ether (Triton X-100; TX) with tau2 abolished its immunoreactivity (IR) in these microglia but not its IR on NFTs. Tau2-immunoreactive bands, exclusively retrieved in Tris-soluble fraction of brain homogenates from ischemic foci, normal human and bovine brains, were of similar electrophoretic mobility, indicating that tau2 IR in these microglia is unrelated to hyperphosphorylation of tau. These tau2-immunoreactive bands except those from bovine brain were abolished in the copresence of TX. This was not due to washing out of tau, because similar immunoreactive bands were detectable with another antitau antibody even under a higher concentration of TX and because washing after TX exposure restored similar tau2 IR both on immunohistochemistry and immunoblot. These findings are explained if tau, modified after ischemia, undergoes a reversible conformational change on TX exposure. Because conformation at Ser101 of bovine tau is crucial for its affinity to tau2, this Ser-like conformation mimicked by its human counterpart Pro may represent pathological modification of tau shared by microglia around ischemic foci and NFTs. Relative resistance of tau2 epitope in NFTs to TX exposure suggests that tau woven into NFTs confers additional stability to this pathological modification on tau2 epitope. Susceptibility of tau2 epitope to TX, seen in these microglia, is shared with glial cytoplasmic inclusions and will show its conformational state to be different from that in NFTs. PMID:14730711

  12. W{right arrow} {tau} {nu} at the Tevatron

    SciTech Connect

    Serban Protopopescu

    1998-12-01

    We present results from the CDF and D0 detectors on the production of W-bosons decaying to {tau}{nu}{sub {tau}} at the FNAL Tevatron from data taken between 1992 and 1996. From CDF comes the first observation of W charge asymmetry in W {yields} {tau}{nu} final states, and from D0 a new measurement of g{sup W}{sub {tau}}/g{sup W}{sub e} , 1.003 {+-} 0.032.

  13. Observation of B{sup +{yields}}D*{sup 0{tau}+{nu}}{sub {tau}}and evidence for B{sup +{yields}}D{sup 0{tau}+{nu}}{sub {tau}}at Belle

    SciTech Connect

    Bozek, A.; Rozanska, M.; Kapusta, P.; Matyja, A.; Ostrowicz, W.; Stypula, J.; Adachi, I.; Higuchi, T.; Iwasaki, Y.; Kichimi, H.; Krokovny, P.; Nakao, M.; Nishida, S.; Nozaki, T.; Sakai, Y.; Schuemann, J.; Trabelsi, K.; Uehara, S.; Uno, S.; Aihara, H.

    2010-10-01

    We present measurements of B{sup +{yields}}D*{sup 0{tau}+{nu}}{sub {tau}}and B{sup +{yields}}D{sup 0{tau}+{nu}}{sub {tau}}decays in a data sample of 657x10{sup 6} BB pairs collected with the Belle detector at the KEKB asymmetric-energy e{sup +}e{sup -} collider. We find 446{sub -56}{sup +58} B{sup +{yields}}D*{sup 0{tau}+{nu}}{sub {tau}}events with a significance of 8.1 standard deviations, and 146{sub -41}{sup +42} B{sup +{yields}}D{sup 0{tau}+{nu}}{sub {tau}}events with a significance of 3.5 standard deviations. The latter signal provides the first evidence for this decay mode. The measured branching fractions are B(B{sup +{yields}}D*{sup 0{tau}+{nu}}{sub {tau}})=(2.12{sub -0.27}{sup +0.28}(stat){+-}0.29(syst))% and B(B{sup +{yields}}D{sup 0{tau}+{nu}}{sub {tau}})=(0.77{+-}0.22(stat){+-}0.12(syst))%.

  14. Recent Results From BaBar in Tau Physics

    SciTech Connect

    Lewczuk, Mateusz; /Victoria U.

    2009-06-25

    The BaBar collaboration has accumulated over 400 million {tau}-pairs which can be used to study charged leptonic and hadronic weak currents to unprecedented precision. This note presents results on lepton universality, measurements of |V{sub us}|, and searches for {tau} decays which violate lepton flavour conservation, or {tau} decays that proceed through a suppressed second class current.

  15. Antisense Reduction of Tau in Adult Mice Protects against Seizures

    PubMed Central

    DeVos, Sarah L.; Goncharoff, Dustin K.; Chen, Guo; Kebodeaux, Carey S.; Yamada, Kaoru; Stewart, Floy R.; Schuler, Dorothy R.; Maloney, Susan E.; Wozniak, David F.; Rigo, Frank; Bennett, C. Frank; Cirrito, John R.; Holtzman, David M.

    2013-01-01

    Tau, a microtubule-associated protein, is implicated in the pathogenesis of Alzheimer's Disease (AD) in regard to both neurofibrillary tangle formation and neuronal network hyperexcitability. The genetic ablation of tau substantially reduces hyperexcitability in AD mouse lines, induced seizure models, and genetic in vivo models of epilepsy. These data demonstrate that tau is an important regulator of network excitability. However, developmental compensation in the genetic tau knock-out line may account for the protective effect against seizures. To test the efficacy of a tau reducing therapy for disorders with a detrimental hyperexcitability profile in adult animals, we identified antisense oligonucleotides that selectively decrease endogenous tau expression throughout the entire mouse CNS—brain and spinal cord tissue, interstitial fluid, and CSF—while having no effect on baseline motor or cognitive behavior. In two chemically induced seizure models, mice with reduced tau protein had less severe seizures than control mice. Total tau protein levels and seizure severity were highly correlated, such that those mice with the most severe seizures also had the highest levels of tau. Our results demonstrate that endogenous tau is integral for regulating neuronal hyperexcitability in adult animals and suggest that an antisense oligonucleotide reduction of tau could benefit those with epilepsy and perhaps other disorders associated with tau-mediated neuronal hyperexcitability. PMID:23904623

  16. Regulation of alternative splicing of tau exon 10.

    PubMed

    Qian, Wei; Liu, Fei

    2014-04-01

    The neuronal microtubule-associated protein tau is abnormally hyperphosphorylated and aggregated into neurofibrillary tangles in the brains of individuals with Alzheimer's disease and related neurodegenerative disorders. The adult human brain expresses six isoforms of tau generated by alternative splicing of exons 2, 3, and 10 of its pre-mRNA. Exon 10 encodes the second microtubule-binding repeat of tau. Its alternative splicing produces tau isoforms with either three or four microtubule-binding repeats, termed 3R-tau and 4Rtau. In the normal adult human brain, the level of 3R-tau is approximately equal to that of 4R-tau. Several silent and intronic mutations of the tau gene associated with FTDP-17T (frontotemporal dementia with Parkinsonism linked to chromosome 17 and specifically characterized by tau pathology) only disrupt exon 10 splicing, but do not influence the primary sequence of the tau protein. Thus, abnormal exon 10 splicing is sufficient to cause neurodegeneration and dementia. Here, we review the regulation of tau exon 10 splicing by cis-elements and trans-factors and summarize all the mutations associated with FTDP-17T and related tauopathies. The findings suggest that correction of exon 10 splicing may be a potential target for tau exon 10 splicing-related tauopathies. PMID:24627328

  17. Estimation of Tau and Phosphorylated Tau181 in Serum of Alzheimer’s Disease and Mild Cognitive Impairment Patients

    PubMed Central

    Shekhar, Shashank; Kumar, Rahul; Rai, Nitish; Kumar, Vijay; Singh, Kusum; Upadhyay, Ashish Datt; Tripathi, Manjari; Dwivedi, Sadanand; Dey, Aparajit B.; Dey, Sharmistha

    2016-01-01

    The elevated level of cerebrospinal fluid (CSF) Tau and phosphorylated Tau181 (p-Tau181) proteins are well established hallmarks of Alzheimer’s disease (AD). Elevated level of p-Tau181 can differentiate AD from other neurodegenerative disease. However, the expression level of these proteins in serum of AD patient is not well set up. This study sought to evaluate the level of Tau and p-Tau181 in serum of AD, and mild cognitive impairment (MCI) patients for an alternative approach to establish protein-based markers by convenient way. Blood samples were collected from 39 AD patients, 37 MCI patients and 37 elderly individuals as controls. The levels of Tau and p-Tau181 in the serum of the different groups were measured by label free real time Surface Plasmon Resonance technology by using specific antibodies, and were further confirmed by the conventional western blot method. An appropriate statistical analysis, including Receiver Operating Characteristic (ROC), was performed. The concentrations of serum Tau and p-Tau181 were significantly higher (p<0.00001) in AD (Tau; 47.49±9.00ng/μL, p-Tau181; 0.161±0.04 ng/μL) compared to MCI (Tau; 39.26±7.78 ng/μL, p-Tau181; 0.135±0.02 ng/μL) and were further higher compared to elderly controls (Tau; 34.92±6.58 ng/μL, p-Tau181; 0.122±0.01 ng/ μL). A significant (p<0.0001) downhill correlation was found between Tau as well as p-Tau181 levels with HMSE and MoCA score. This study for the first time reports the concentration of Tau and p-Tau181 in serum of AD and MCI patients. The cutoff values of Tau and p-Tau181 of AD and MCI patients with sensitivity and specificity reveal that serum level of these proteins can be used as a predictive marker for AD and MCI. PMID:27459603

  18. Optical variability in the unusual K5 V infrared-excess star HD 98800

    NASA Technical Reports Server (NTRS)

    Henry, Gregory W.; Hall, Douglas S.

    1994-01-01

    The dusty infrared-excess star HD 98800 (K5 V) was observed for several weeks in the spring of 1993 by the Vanderbilt/Tennessee State 0.4 m automatic photoelectric telescope. It was found to be a variable star with an amplitude of 0.07 mag in V and a period of 14.7 days. We show, by comparison with other chromospherically active variable stars and constant stars with good observational histories, that the Rossby number for HD 98800, determined to be 0.30, places it well within the regime of stars whose convective envelopes and rotation rates combine to drive a magnetic dynamo strong enough to generate photometrically observable starspots. The light curve suggests at least two large spots at somewhat different longitudes on HD 98800, one of which could be as large as 16 deg in radius.

  19. Final report. SIM comparison in mass standards SIM.M.M-K5

    NASA Astrophysics Data System (ADS)

    Becerra, L. O.; Peña, L. M.; Luján, L.; Díaz, J. C.; Centeno, L. M.; Loayza, V.; Cacais, F.; Ramos, O.; Rodriguez, S.; Garcia, Fr; Garcia, Fe; Leyton, F.; Santo, C.; Caceres, J.; Kornblit, F.; Leiblich, J.; Jacques, C.

    2016-01-01

    This report summarizes the results of a SIM comparison in masss carried out between 7 NMIs. Five mass standards with nominal values 2 kg, 200 g, 50 g, 1 g and 200 mg have been circulated by the NMIs. The results reported by the participants are consistent with each other and with the key comparison reference valu of the comparison CCM.M-K5 to which the present comparison has been linked. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  20. Riluzole rescues glutamate alterations, cognitive deficits, and tau pathology associated with P301L tau expression.

    PubMed

    Hunsberger, Holly C; Weitzner, Daniel S; Rudy, Carolyn C; Hickman, James E; Libell, Eric M; Speer, Rebecca R; Gerhardt, Greg A; Reed, Miranda N

    2015-10-01

    Hyperexcitability of the hippocampus is a commonly observed phenomenon in the years preceding a diagnosis of Alzheimer's disease (AD). Our previous work suggests a dysregulation in glutamate neurotransmission may mediate this hyperexcitability, and glutamate dysregulation correlates with cognitive deficits in the rTg(TauP301L)4510 mouse model of AD. To determine whether improving glutamate regulation would attenuate cognitive deficits and AD-related pathology, TauP301L mice were treated with riluzole (~ 12.5 mg/kg/day p.o.), an FDA-approved drug for amyotrophic lateral sclerosis that lowers extracellular glutamate levels. Riluzole-treated TauP301L mice exhibited improved performance in the water radial arm maze and the Morris water maze, associated with a decrease in glutamate release and an increase in glutamate uptake in the dentate gyrus, cornu ammonis 3 (CA3), and cornu ammonis 1 (CA1) regions of the hippocampus. Riluzole also attenuated the TauP301L-mediated increase in hippocampal vesicular glutamate transporter 1, which packages glutamate into vesicles and influences glutamate release; and the TauP301L-mediated decrease in hippocampal glutamate transporter 1, the major transporter responsible for removing glutamate from the extracellular space. The TauP301L-mediated reduction in PSD-95 expression, a marker of excitatory synapses in the hippocampus, was also rescued by riluzole. Riluzole treatment reduced total levels of tau, as well as the pathological phosphorylation and conformational changes in tau associated with the P301L mutation. These findings open new opportunities for the development of clinically applicable therapeutic approaches to regulate glutamate in vulnerable circuits for those at risk for the development of AD. PMID:26146790

  1. Search for a low-mass higgs boson in Upsilon(3S)-->gammaA(0), A(0)-->tau(+)tau(-) at BABAR.

    PubMed

    Aubert, B; Karyotakis, Y; Lees, J P; Poireau, V; Prencipe, E; Prudent, X; Tisserand, V; Tico, J Garra; Grauges, E; Martinelli, M; Palano, A; Pappagallo, M; Eigen, G; Stugu, B; Sun, L; Battaglia, M; Brown, D N; Kerth, L T; Kolomensky, Yu G; Lynch, G; Osipenkov, I L; Tackmann, K; Tanabe, T; Hawkes, C M; Soni, N; Watson, A T; Koch, H; Schroeder, T; Asgeirsson, D J; Fulsom, B G; Hearty, C; Mattison, T S; McKenna, J A; Barrett, M; Khan, A; Randle-Conde, A; Blinov, V E; Bukin, A D; Buzykaev, A R; Druzhinin, V P; Golubev, V B; Onuchin, A P; Serednyakov, S I; Skovpen, Yu I; Solodov, E P; Todyshev, K Yu; Bondioli, M; Curry, S; Eschrich, I; Kirkby, D; Lankford, A J; Lund, P; Mandelkern, M; Martin, E C; Stoker, D P; Atmacan, H; Gary, J W; Liu, F; Long, O; Vitug, G M; Yasin, Z; Sharma, V; Campagnari, C; Hong, T M; Kovalskyi, D; Mazur, M A; Richman, J D; Beck, T W; Eisner, A M; Heusch, C A; Kroseberg, J; Lockman, W S; Martinez, A J; Schalk, T; Schumm, B A; Seiden, A; Wang, L; Winstrom, L O; Cheng, C H; Doll, D A; Echenard, B; Fang, F; Hitlin, D G; Narsky, I; Ongmongkolkul, P; Piatenko, T; Porter, F C; Andreassen, R; Mancinelli, G; Meadows, B T; Mishra, K; Sokoloff, M D; Bloom, P C; Ford, W T; Gaz, A; Hirschauer, J F; Nagel, M; Nauenberg, U; Smith, J G; Wagner, S R; Ayad, R; Toki, W H; Wilson, R J; Feltresi, E; Hauke, A; Jasper, H; Karbach, T M; Merkel, J; Petzold, A; Spaan, B; Wacker, K; Kobel, M J; Nogowski, R; Schubert, K R; Schwierz, R; Bernard, D; Latour, E; Verderi, M; Clark, P J; Playfer, S; Watson, J E; Andreotti, M; Bettoni, D; Bozzi, C; Calabrese, R; Cecchi, A; Cibinetto, G; Fioravanti, E; Franchini, P; Luppi, E; Munerato, M; Negrini, M; Petrella, A; Piemontese, L; Santoro, V; Baldini-Ferroli, R; Calcaterra, A; de Sangro, R; Finocchiaro, G; Pacetti, S; Patteri, P; Peruzzi, I M; Piccolo, M; Rama, M; Zallo, A; Contri, R; Guido, E; Lo Vetere, M; Monge, M R; Passaggio, S; Patrignani, C; Robutti, E; Tosi, S; Chaisanguanthum, K S; Morii, M; Adametz, A; Marks, J; Schenk, S; Uwer, U; Bernlochner, F U; Klose, V; Lacker, H M; Lueck, T; Volk, A; Bard, D J; Dauncey, P D; Tibbetts, M; Behera, P K; Charles, M J; Mallik, U; Cochran, J; Crawley, H B; Dong, L; Eyges, V; Meyer, W T; Prell, S; Rosenberg, E I; Rubin, A E; Gao, Y Y; Gritsan, A V; Guo, Z J; Arnaud, N; Béquilleux, J; D'Orazio, A; Davier, M; Derkach, D; da Costa, J Firmino; Grosdidier, G; Le Diberder, F; Lepeltier, V; Lutz, A M; Malaescu, B; Pruvot, S; Roudeau, P; Schune, M H; Serrano, J; Sordini, V; Stocchi, A; Wormser, G; Lange, D J; Wright, D M; Bingham, I; Burke, J P; Chavez, C A; Fry, J R; Gabathuler, E; Gamet, R; Hutchcroft, D E; Payne, D J; Touramanis, C; Bevan, A J; Clarke, C K; Di Lodovico, F; Sacco, R; Sigamani, M; Cowan, G; Paramesvaran, S; Wren, A C; Brown, D N; Davis, C L; Denig, A G; Fritsch, M; Gradl, W; Hafner, A; Alwyn, K E; Bailey, D; Barlow, R J; Jackson, G; Lafferty, G D; West, T J; Yi, J I; Anderson, J; Chen, C; Jawahery, A; Roberts, D A; Simi, G; Tuggle, J M; Dallapiccola, C; Salvati, E; Cowan, R; Dujmic, D; Fisher, P H; Henderson, S W; Sciolla, G; Spitznagel, M; Yamamoto, R K; Zhao, M; Patel, P M; Robertson, S H; Schram, M; Biassoni, P; Lazzaro, A; Lombardo, V; Palombo, F; Stracka, S; Cremaldi, L; Godang, R; Kroeger, R; Sonnek, P; Summers, D J; Zhao, H W; Simard, M; Taras, P; Nicholson, H; De Nardo, G; Lista, L; Monorchio, D; Onorato, G; Sciacca, C; Raven, G; Snoek, H L; Jessop, C P; Knoepfel, K J; Losecco, J M; Wang, W F; Corwin, L A; Honscheid, K; Kagan, H; Kass, R; Morris, J P; Rahimi, A M; Sekula, S J; Wong, Q K; Blount, N L; Brau, J; Frey, R; Igonkina, O; Kolb, J A; Lu, M; Rahmat, R; Sinev, N B; Strom, D; Strube, J; Torrence, E; Castelli, G; Gagliardi, N; Margoni, M; Morandin, M; Posocco, M; Rotondo, M; Simonetto, F; Stroili, R; Voci, C; Del Amo Sanchez, P; Ben-Haim, E; Bonneaud, G R; Briand, H; Chauveau, J; Hamon, O; Leruste, Ph; Marchiori, G; Ocariz, J; Perez, A; Prendki, J; Sitt, S; Gladney, L; Biasini, M; Manoni, E; Angelini, C; Batignani, G; Bettarini, S; Calderini, G; Carpinelli, M; Cervelli, A; Forti, F; Giorgi, M A; Lusiani, A; Morganti, M; Neri, N; Paoloni, E; Rizzo, G; Walsh, J J; Lopes Pegna, D; Lu, C; Olsen, J; Smith, A J S; Telnov, A V; Anulli, F; Baracchini, E; Cavoto, G; Faccini, R; Ferrarotto, F; Ferroni, F; Gaspero, M; Jackson, P D; Gioi, L Li; Mazzoni, M A; Morganti, S; Piredda, G; Renga, F; Voena, C; Ebert, M; Hartmann, T; Schröder, H; Waldi, R; Adye, T; Franek, B; Olaiya, E O; Wilson, F F; Emery, S; Esteve, L; Hamel de Monchenault, G; Kozanecki, W; Vasseur, G; Yèche, Ch; Zito, M; Allen, M T; Aston, D; Bartoldus, R; Benitez, J F; Cenci, R; Coleman, J P; Convery, M R; Dingfelder, J C; Dorfan, J; Dubois-Felsmann, G P; Dunwoodie, W; Field, R C; Sevilla, M Franco; Gabareen, A M; Graham, M T; Grenier, P; Hast, C; Innes, W R; Kaminski, J; Kelsey, M H; Kim, H; Kim, P; Kocian, M L; Leith, D W G S; Li, S; Lindquist, B; Luitz, S; Luth, V; Lynch, H L; Macfarlane, D B; Marsiske, H; Messner, R; Muller, D R; Neal, H; Nelson, S; O'Grady, C P; Ofte, I; Perl, M; Ratcliff, B N; Roodman, A; Salnikov, A A; Schindler, R H; Schwiening, J; Snyder, A; Su, D; Sullivan, M K; Suzuki, K; Swain, S K; Thompson, J M; Va'vra, J; Wagner, A P; Weaver, M; West, C A; Wisniewski, W J; Wittgen, M; Wright, D H; Wulsin, H W; Yarritu, A K; Young, C C; Ziegler, V; Chen, X R; Liu, H; Park, W; Purohit, M V; White, R M; Wilson, J R; Bellis, M; Burchat, P R; Edwards, A J; Miyashita, T S; Ahmed, S; Alam, M S; Ernst, J A; Pan, B; Saeed, M A; Zain, S B; Soffer, A; Spanier, S M; Wogsland, B J; Eckmann, R; Ritchie, J L; Ruland, A M; Schilling, C J; Schwitters, R F; Wray, B C; Drummond, B W; Izen, J M; Lou, X C; Bianchi, F; Gamba, D; Pelliccioni, M; Bomben, M; Bosisio, L; Cartaro, C; Della Ricca, G; Lanceri, L; Vitale, L; Azzolini, V; Lopez-March, N; Martinez-Vidal, F; Milanes, D A; Oyanguren, A; Albert, J; Banerjee, Sw; Bhuyan, B; Choi, H H F; Hamano, K; King, G J; Kowalewski, R; Lewczuk, M J; Nugent, I M; Roney, J M; Sobie, R J; Gershon, T J; Harrison, P F; Ilic, J; Latham, T E; Mohanty, G B; Puccio, E M T; Band, H R; Chen, X; Dasu, S; Flood, K T; Pan, Y; Prepost, R; Vuosalo, C O; Wu, S L

    2009-10-30

    We search for a light Higgs boson A0 in the radiative decay Upsilon(3S)-->gammaA(0), A(0)-->tau+tau-, tau+-->e+nu(e)nu(tau), or tau+-->mu+nu(mu)nu(tau). The data sample contains 122x10(6) Upsilon(3S) events recorded with the BABAR detector. We find no evidence for a narrow structure in the studied tau+tau- invariant mass region of 4.03tau+tau-)<10.10 GeV/c2. We exclude at the 90% confidence level (C.L.) a low-mass Higgs boson decaying to tau+tau- with a product branching fraction B(Upsilon(3S)-->gammaA(0))xB(A(0)-->tau+tau-)>(1.5-16)x10(-5) across the m(tau+tau-) range. We also set a 90% C.L. upper limit on the tau+tau- decay of the eta(b) at B(eta(b)-->tau+tau-)<8%. PMID:19905799

  2. Trans-cellular propagation of Tau aggregation by fibrillar species.

    PubMed

    Kfoury, Najla; Holmes, Brandon B; Jiang, Hong; Holtzman, David M; Diamond, Marc I

    2012-06-01

    Aggregation of the microtubule associated protein Tau is associated with several neurodegenerative disorders, including Alzheimer disease and frontotemporal dementia. In Alzheimer disease, Tau pathology spreads progressively throughout the brain, possibly along existing neural networks. However, it is still unclear how the propagation of Tau misfolding occurs. Intriguingly, in animal models, vaccine-based therapies have reduced Tau and synuclein pathology by uncertain mechanisms, given that these proteins are intracellular. We have previously speculated that trans-cellular propagation of misfolding could be mediated by a process similar to prion pathogenesis, in which fibrillar Tau aggregates spread pathology from cell to cell. However, there has been little evidence to demonstrate true trans-cellular propagation of Tau misfolding, in which Tau aggregates from one cell directly contact Tau protein in the recipient cell to trigger further aggregation. Here we have observed that intracellular Tau fibrils are directly released into the medium and then taken up by co-cultured cells. Internalized Tau aggregates induce fibrillization of intracellular Tau in these naive recipient cells via direct protein-protein contact that we demonstrate using FRET. Tau aggregation can be amplified across several generations of cells. An anti-Tau monoclonal antibody blocks Tau aggregate propagation by trapping fibrils in the extracellular space and preventing their uptake. Thus, propagation of Tau protein misfolding among cells can be mediated by release and subsequent uptake of fibrils that directly contact native protein in recipient cells. These results support the model of aggregate propagation by templated conformational change and suggest a mechanism for vaccine-based therapies in neurodegenerative diseases. PMID:22461630

  3. Resolved multifrequency radio observations of GG Tau

    SciTech Connect

    Andrews, Sean M.; Birnstiel, T.; Rosenfeld, K. A.; Wilner, D. J.; Chandler, Claire J.; Pérez, L. M.; Isella, Andrea; Ricci, L.; Carpenter, J. M.; Calvet, N.; Corder, S. A.; Deller, A. T.; Dullemond, C. P.; Greaves, J. S.; Harris, R. J.; Henning, Th.; Linz, H.; Kwon, W.; Lazio, J.; Mundy, L. G.; and others

    2014-06-01

    We present subarcsecond resolution observations of continuum emission associated with the GG Tau quadruple star system at wavelengths of 1.3, 2.8, 7.3, and 50 mm. These data confirm that the GG Tau A binary is encircled by a circumbinary ring at a radius of 235 AU with a FWHM width of ∼60 AU. We find no clear evidence for a radial gradient in the spectral shape of the ring, suggesting that the particle size distribution is spatially homogeneous on angular scales ≳0.''1. A central point source, likely associated with the primary component (GG Tau Aa), exhibits a composite spectrum from dust and free-free emission. Faint emission at 7.3 mm is observed toward the low-mass star GG Tau Ba, although its origin remains uncertain. Using these measurements of the resolved, multifrequency emission structure of the GG Tau A system, models of the far-infrared to radio spectrum are developed to place constraints on the grain size distribution and dust mass in the circumbinary ring. The non-negligible curvature present in the ring spectrum implies a maximum particle size of 1-10 mm, although we are unable to place strong constraints on the distribution shape. The corresponding dust mass is 30-300 M {sub ⊕}, at a temperature of 20-30 K. We discuss how this significant concentration of relatively large particles in a narrow ring at a large radius might be produced in a local region of higher gas pressures (i.e., a particle 'trap') located near the inner edge of the circumbinary disk.

  4. EFFECT OF DUST ON Ly{alpha} PHOTON TRANSFER IN AN OPTICALLY THICK HALO

    SciTech Connect

    Yang Yang; Shu Chiwang; Roy, Ishani; Fang Lizhi

    2011-10-01

    We investigate the effects of dust on Ly{alpha} photons emergent from an optically thick medium by solving the integro-differential equation of radiative transfer of resonant photons. To solve the differential equations numerically, we use the weighted essentially non-oscillatory method. Although the effects of dust on radiative transfer are well known, the resonant scattering of Ly{alpha} photons makes the problem non-trivial. For instance, if the medium has an optical depth of dust absorption and scattering of {tau}{sub a} >> 1, {tau} >> 1, and {tau} >> {tau}{sub a}, the effective absorption optical depth in a random walk scenario would be equal to {radical}({tau}{sub a}({tau}{sub a}+{tau})). We show, however, that for a resonant scattering at frequency {nu}{sub 0}, the effective absorption optical depth would be even larger than {tau}({nu}{sub 0}). If the cross section of dust scattering and absorption is frequency-independent, the double-peaked structure of the frequency profile given by the resonant scattering is basically dust-independent. That is, dust causes neither narrowing nor widening of the width of the double-peaked profile. One more result is that the timescales of the Ly{alpha} photon transfer in an optically thick halo are also basically independent of the dust scattering, even when the scattering is anisotropic. This is because those timescales are mainly determined by the transfer in the frequency space, while dust scattering, either isotropic or anisotropic, does not affect the behavior of the transfer in the frequency space when the cross section of scattering is wavelength-independent. This result does not support the speculation that dust will lead to the smoothing of the brightness distribution of a Ly{alpha} photon source with an optically thick halo.

  5. Phosphorylation of tau by glycogen synthase kinase 3beta affects the ability of tau to promote microtubule self-assembly.

    PubMed Central

    Utton, M A; Vandecandelaere, A; Wagner, U; Reynolds, C H; Gibb, G M; Miller, C C; Bayley, P M; Anderton, B H

    1997-01-01

    To study the effects of phosphorylation by glycogen synthase kinase-3beta (GSK-3beta) on the ability of the microtubule-associated protein tau to promote microtubule self-assembly, tau isoform 1 (foetal tau) and three mutant forms of this tau isoform were investigated. The three mutant forms of tau had the following serine residues, known to be phosphorylated by GSK-3, replaced with alanine residues so as to preclude their phosphorylation: (1) Ser-199 and Ser-202 (Ser-199/202-->Ala), (2) Ser-235 (Ser-235-->Ala) and (3) Ser-396 and Ser-404 (Ser-396/404-->Ala). Wild-type tau and the mutant forms of tau were phosphorylated with GSK-3beta, and their ability to promote microtubule self-assembly was compared with the corresponding non-phosphorylated tau species. In the non-phosphorylated form, wild-type tau and all of the mutants affected the mean microtubule length and number concentrations of assembled microtubules in a manner consistant with enhanced microtubule nucleation. Phosphorylation of these tau species with GSK-3beta consistently reduced the ability of a given tau species to promote microtubule self-assembly, although the affinity of the tau for the microtubules was not greatly affected by phosphorylation since the tau species remained largely associated with the microtubules. This suggests that the regulation of microtubule assembly can be controlled by phosphorylation of tau at sites accessible to GSK-3beta by a mechanism that does not necessarily involve the dissociation of tau from the microtubules. PMID:9169608

  6. Curcumin Suppresses Soluble Tau Dimers and Corrects Molecular Chaperone, Synaptic, and Behavioral Deficits in Aged Human Tau Transgenic Mice*

    PubMed Central

    Ma, Qiu-Lan; Zuo, Xiaohong; Yang, Fusheng; Ubeda, Oliver J.; Gant, Dana J.; Alaverdyan, Mher; Teng, Edmond; Hu, Shuxin; Chen, Ping-Ping; Maiti, Panchanan; Teter, Bruce; Cole, Greg M.; Frautschy, Sally A.

    2013-01-01

    The mechanisms underlying Tau-related synaptic and cognitive deficits and the interrelationships between Tau species, their clearance pathways, and synaptic impairments remain poorly understood. To gain insight into these mechanisms, we examined these interrelationships in aged non-mutant genomic human Tau mice, with established Tau pathology and neuron loss. We also examined how these interrelationships changed with an intervention by feeding mice either a control diet or one containing the brain permeable beta-amyloid and Tau aggregate binding molecule curcumin. Transgene-dependent elevations in soluble and insoluble phospho-Tau monomer and soluble Tau dimers accompanied deficits in behavior, hippocampal excitatory synaptic markers, and molecular chaperones (heat shock proteins (HSPs)) involved in Tau degradation and microtubule stability. In human Tau mice but not control mice, HSP70, HSP70/HSP72, and HSP90 were reduced in membrane-enriched fractions but not in cytosolic fractions. The synaptic proteins PSD95 and NR2B were reduced in dendritic fields and redistributed into perikarya, corresponding to changes observed by immunoblot. Curcumin selectively suppressed levels of soluble Tau dimers, but not of insoluble and monomeric phospho-Tau, while correcting behavioral, synaptic, and HSP deficits. Treatment increased PSD95 co-immunoprecipitating with NR2B and, independent of transgene, increased HSPs implicated in Tau clearance. It elevated HSP90 and HSC70 without increasing HSP mRNAs; that is, without induction of the heat shock response. Instead curcumin differentially impacted HSP90 client kinases, reducing Fyn without reducing Akt. In summary, curcumin reduced soluble Tau and elevated HSPs involved in Tau clearance, showing that even after tangles have formed, Tau-dependent behavioral and synaptic deficits can be corrected. PMID:23264626

  7. The Disk around the Brown Dwarf KPNO Tau 3

    NASA Astrophysics Data System (ADS)

    Broekhoven-Fiene, Hannah; Matthews, Brenda; Duchêne, Gaspard; Di Francesco, James; Scholz, Aleks; Chrysostomou, Antonio; Jayawardhana, Ray

    2014-07-01

    We present submillimeter observations of the young brown dwarfs KPNO Tau 1, KPNO Tau 3, and KPNO Tau 6 at 450 μm and 850 μm taken with the Submillimetre Common-User Bolometer Array on the James Clerk Maxwell Telescope. KPNO Tau 3 and KPNO Tau 6 have been previously identified as Class II objects hosting accretion disks, whereas KPNO Tau 1 has been identified as a Class III object and shows no evidence of circumsubstellar material. Our 3σ detection of cold dust around KPNO Tau 3 implies a total disk mass of (4.0 ± 1.1) × 10-4 M ⊙ (assuming a gas to dust ratio of 100:1). We place tight constraints on any disks around KPNO Tau 1 or KPNO Tau 6 of <2.1 × 10-4 M ⊙ and <2.7 × 10-4 M ⊙, respectively. Modeling the spectral energy distribution of KPNO Tau 3 and its disk suggests the disk properties (geometry, dust mass, and grain size distribution) are consistent with observations of other brown dwarf disks and low-mass T-Tauri stars. In particular, the disk-to-host mass ratio for KPNO Tau 3 is congruent with the scenario that at least some brown dwarfs form via the same mechanism as low-mass stars.

  8. Evidence for two distinct binding sites for tau on microtubules

    PubMed Central

    Makrides, Victoria; Massie, Michelle R.; Feinstein, Stuart C.; Lew, John

    2004-01-01

    The microtubule-associated protein tau regulates diverse and essential microtubule functions, from the nucleation and promotion of microtubule polymerization to the regulation of microtubule polarity and dynamics, as well as the spacing and bundling of axonal microtubules. Thermodynamic studies show that tau interacts with microtubules in the low- to mid-nanomolar range, implying moderate binding affinity. At the same time, it is well established that microtubule-bound tau does not undergo exchange with the bulk medium readily, suggesting that the tau-microtubule interaction is essentially irreversible. Given this dilemma, we investigated the mechanism of interaction between tau and microtubules in kinetic detail. Stopped-flow kinetic analysis reveals moderate binding affinity between tau and preassembled microtubules and rapid dissociation/association kinetics. In contrast, when microtubules are generated by copolymerization of tubulin and tau, a distinct population of microtubule-bound tau is observed, the binding of which seems irreversible. We propose that reversible binding occurs between tau and the surface of preassembled microtubules, whereas irreversible binding results when tau is coassembled with tubulin into a tau-microtubule copolymer. Because the latter is expected to be physiologically relevant, its characterization is of central importance. PMID:15096589

  9. The disk around the brown dwarf KPNO Tau 3

    SciTech Connect

    Broekhoven-Fiene, Hannah; Matthews, Brenda; Di Francesco, James; Duchêne, Gaspard; Scholz, Aleks; Chrysostomou, Antonio; Jayawardhana, Ray

    2014-07-10

    We present submillimeter observations of the young brown dwarfs KPNO Tau 1, KPNO Tau 3, and KPNO Tau 6 at 450 μm and 850 μm taken with the Submillimetre Common-User Bolometer Array on the James Clerk Maxwell Telescope. KPNO Tau 3 and KPNO Tau 6 have been previously identified as Class II objects hosting accretion disks, whereas KPNO Tau 1 has been identified as a Class III object and shows no evidence of circumsubstellar material. Our 3σ detection of cold dust around KPNO Tau 3 implies a total disk mass of (4.0 ± 1.1) × 10{sup –4} M{sub ☉} (assuming a gas to dust ratio of 100:1). We place tight constraints on any disks around KPNO Tau 1 or KPNO Tau 6 of <2.1 × 10{sup –4} M{sub ☉} and <2.7 × 10{sup –4} M{sub ☉}, respectively. Modeling the spectral energy distribution of KPNO Tau 3 and its disk suggests the disk properties (geometry, dust mass, and grain size distribution) are consistent with observations of other brown dwarf disks and low-mass T-Tauri stars. In particular, the disk-to-host mass ratio for KPNO Tau 3 is congruent with the scenario that at least some brown dwarfs form via the same mechanism as low-mass stars.

  10. Dimer model for Tau proteins bound in microtubule bundles

    NASA Astrophysics Data System (ADS)

    Hall, Natalie; Kluber, Alexander; Hayre, N. Robert; Singh, Rajiv; Cox, Daniel

    2013-03-01

    The microtubule associated protein tau is important in nucleating and maintaining microtubule spacing and structure in neuronal axons. Modification of tau is implicated as a later stage process in Alzheimer's disease, but little is known about the structure of tau in microtubule bundles. We present preliminary work on a proposed model for tau dimers in microtubule bundles (dimers are the minimal units since there is one microtubule binding domain per tau). First, a model of tau monomer was created and its characteristics explored using implicit solvent molecular dynamics simulation. Multiple simulations yield a partially collapsed form with separate positively/negatively charged clumps, but which are a factor of two smaller than required by observed microtubule spacing. We argue that this will elongate in dimer form to lower electrostatic energy at a cost of entropic ``spring'' energy. We will present preliminary results on steered molecular dynamics runs on tau dimers to estimate the actual force constant. Supported by US NSF Grant DMR 1207624.

  11. APP metabolism regulates tau proteostasis in human cerebral cortex neurons.

    PubMed

    Moore, Steven; Evans, Lewis D B; Andersson, Therese; Portelius, Erik; Smith, James; Dias, Tatyana B; Saurat, Nathalie; McGlade, Amelia; Kirwan, Peter; Blennow, Kaj; Hardy, John; Zetterberg, Henrik; Livesey, Frederick J

    2015-05-01

    Accumulation of Aβ peptide fragments of the APP protein and neurofibrillary tangles of the microtubule-associated protein tau are the cellular hallmarks of Alzheimer's disease (AD). To investigate the relationship between APP metabolism and tau protein levels and phosphorylation, we studied human-stem-cell-derived forebrain neurons with genetic forms of AD, all of which increase the release of pathogenic Aβ peptides. We identified marked increases in intracellular tau in genetic forms of AD that either mutated APP or increased its dosage, suggesting that APP metabolism is coupled to changes in tau proteostasis. Manipulating APP metabolism by β-secretase and γ-secretase inhibition, as well as γ-secretase modulation, results in specific increases and decreases in tau protein levels. These data demonstrate that APP metabolism regulates tau proteostasis and suggest that the relationship between APP processing and tau is not mediated solely through extracellular Aβ signaling to neurons. PMID:25921538

  12. PE859, a Novel Tau Aggregation Inhibitor, Reduces Aggregated Tau and Prevents Onset and Progression of Neural Dysfunction In Vivo

    PubMed Central

    Okuda, Michiaki; Hijikuro, Ichiro; Fujita, Yuki; Wu, Xiaofeng; Nakayama, Shinichi; Sakata, Yoko; Noguchi, Yuji; Ogo, Makoto; Akasofu, Shigeru; Ito, Yoshimasa; Soeda, Yoshiyuki; Tsuchiya, Nobuhiko; Tanaka, Naoki; Takahashi, Takashi; Sugimoto, Hachiro

    2015-01-01

    In tauopathies, a neural microtubule-associated protein tau (MAPT) is abnormally aggregated and forms neurofibrillary tangle. Therefore, inhibition of the tau aggregation is one of the key approaches for the treatment of these diseases. Here, we have identified a novel tau aggregation inhibitor, PE859. An oral administration of PE859 resulted in the significant reduction of sarkosyl-insoluble aggregated tau along with the prevention of onset and progression of the motor dysfunction in JNPL3 P301L-mutated human tau transgenic mice. These results suggest that PE859 is useful for the treatment of tauopathies. PMID:25659102

  13. Tau Monoclonal Antibody Generation Based on Humanized Yeast Models

    PubMed Central

    Rosseels, Joëlle; Van den Brande, Jeff; Violet, Marie; Jacobs, Dirk; Grognet, Pierre; Lopez, Juan; Huvent, Isabelle; Caldara, Marina; Swinnen, Erwin; Papegaey, Anthony; Caillierez, Raphaëlle; Buée-Scherrer, Valerie; Engelborghs, Sebastiaan; Lippens, Guy; Colin, Morvane; Buée, Luc; Galas, Marie-Christine; Vanmechelen, Eugeen; Winderickx, Joris

    2015-01-01

    A link between Tau phosphorylation and aggregation has been shown in different models for Alzheimer disease, including yeast. We used human Tau purified from yeast models to generate new monoclonal antibodies, of which three were further characterized. The first antibody, ADx201, binds the Tau proline-rich region independently of the phosphorylation status, whereas the second, ADx215, detects an epitope formed by the Tau N terminus when Tau is not phosphorylated at Tyr18. For the third antibody, ADx210, the binding site could not be determined because its epitope is probably conformational. All three antibodies stained tangle-like structures in different brain sections of THY-Tau22 transgenic mice and Alzheimer patients, and ADx201 and ADx210 also detected neuritic plaques in the cortex of the patient brains. In hippocampal homogenates from THY-Tau22 mice and cortex homogenates obtained from Alzheimer patients, ADx215 consistently stained specific low order Tau oligomers in diseased brain, which in size correspond to Tau dimers. ADx201 and ADx210 additionally reacted to higher order Tau oligomers and presumed prefibrillar structures in the patient samples. Our data further suggest that formation of the low order Tau oligomers marks an early disease stage that is initiated by Tau phosphorylation at N-terminal sites. Formation of higher order oligomers appears to require additional phosphorylation in the C terminus of Tau. When used to assess Tau levels in human cerebrospinal fluid, the antibodies permitted us to discriminate patients with Alzheimer disease or other dementia like vascular dementia, indicative that these antibodies hold promising diagnostic potential. PMID:25540200

  14. Alpha Thalassemia

    MedlinePlus

    ... an apparently normal individual has a child with hemoglobin H disease or alpha thalassemia minor. It can ... gene on one chromosome 25% 25% 25% 25% hemoglobin H disease there is a 25% chance with ...

  15. Scaling and organization of electroencephalographic background activity and alpha rhythm in healthy young adults.

    PubMed

    Lin, D C; Sharif, A; Kwan, H C

    2006-11-01

    The coexistence of the broad-band fluctuation and alpha rhythm of the brain dynamics is studied based on the zero-crossing property of the local electroencephalographic (EEG) recording in eyes closed and eyes open. A two-component zero-crossing scenario, consisting of a broad-band fractal and narrow-band rhythm components, is assumed. Scaling is found in the power law distribution p(tau) approximately tau(-nu) of the crossing time interval tau of the broad-band fluctuation. In alpha dominant brain state, the alpha rhythm interval L also exhibits scaling in the form of power law distribution: p(L) approximately L(phi). Our main result is the relationship nu + phi approximately 3 that characterizes the organization of these two prominent features of the brain dynamics. The possible role of self-organized criticality of punctuated equilibrium in this organization is discussed. PMID:16897091

  16. Calorie restriction does not restore brain mitochondrial function in P301L tau mice, but it does decrease mitochondrial F0F1-ATPase activity.

    PubMed

    Delic, Vedad; Brownlow, Milene; Joly-Amado, Aurelie; Zivkovic, Sandra; Noble, Kenyaria; Phan, Tam-Anh; Ta, Yen; Zhang, Yumeng; Bell, Stephen D; Kurien, Crupa; Reynes, Christian; Morgan, Dave; Bradshaw, Patrick C

    2015-07-01

    Calorie restriction (CR) has been shown to increase lifespan and delay aging phenotypes in many diverse eukaryotic species. In mouse models of Alzheimer's disease (AD), CR has been shown to decrease amyloid-beta and hyperphosphorylated tau levels and preserve cognitive function. Overexpression of human mutant tau protein has been shown to induce deficits in mitochondrial electron transport chain complex I activity. Therefore, experiments were performed to determine the effects of 4-month CR on brain mitochondrial function in Tg4510 mice, which express human P301L tau. Expression of mutant tau led to decreased ADP-stimulated respiratory rates, but not uncoupler-stimulated respiratory rates. The membrane potential was also slightly higher in mitochondria from the P301L tau mice. As shown previously, tau expression decreased mitochondrial complex I activity. The decreased complex I activity, decreased ADP-stimulated respiratory rate, and increased mitochondrial membrane potential occurring in mitochondria from Tg4510 mice were not restored by CR. However, the CR diet did result in a genotype independent decrease in mitochondrial F0F1-ATPase activity. This decrease in F0F1-ATPase activity was not due to lowered levels of the alpha or beta subunits of F0F1-ATPase. The possible mechanisms through which CR reduces the F0F1-ATPase activity in brain mitochondria are discussed. PMID:26048366

  17. Can numerical modeling help understand the fate of tau protein in the axon terminal?

    PubMed

    Kuznetsov, I A; Kuznetsov, A V

    2016-01-01

    In this paper, we used mathematical modeling to investigate the fate of tau protein in the axon terminal. We developed a comprehensive model of tau transport that accounts for transport of cytosolic tau by diffusion, diffusion transport of microtubule (MT)-bound tau along the MT lattice, active motor-driven transport of MT-bound tau via slow axonal transport mechanism, and degradation of tau in the axon due to tau's finite half-life. We investigated the effect of different assumptions concerning the fate of tau in the terminal on steady-state transport of tau in the axon. In particular, we studied two possible scenarios: (i) tau is destroyed in the terminal and (ii) there is no tau destruction in the terminal, and to avoid tau accumulation we postulated zero flux of tau at the terminal. We found that the tau concentration and percentage of MT-bound tau are not very sensitive to the assumption concerning the fate of tau in the terminal, but the tau's flux and average velocity of tau transport are very sensitive to this assumption. This suggests that measuring the velocity of tau transport and comparing it with the results of mathematical modeling for different assumptions concerning tau's fate in the terminal can provide information concerning what happens to tau in the terminal. PMID:25563412

  18. Expression, purification and crystallization of a human tau-tubulin kinase 2 that phosphorylates tau protein

    SciTech Connect

    Kitano-Takahashi, Michiko; Morita, Hiroyuki; Kondo, Shin; Tomizawa, Kayoko; Kato, Ryohei; Tanio, Michikazu; Shirota, Yoshiko; Takahashi, Hiroshi; Sugio, Shigetoshi; Kohno, Toshiyuki

    2007-07-01

    The kinase domain (residues 1–331) of human tau-tubulin kinase 2 was expressed in insect cells, purified and crystallized. Diffraction data have been collected to 2.9 Å resolution. Tau-tubulin kinase 2 (TTBK2) is a Ser/Thr kinase that putatively phosphorylates residues Ser208 and Ser210 (numbered according to a 441-residue human tau isoform) in tau protein. Functional analyses revealed that a recombinant kinase domain (residues 1–331) of human TTBK2 expressed in insect cells with a baculovirus overexpression system retains kinase activity for tau protein. The kinase domain of TTBK2 was crystallized using the hanging-drop vapour-diffusion method. The crystals belong to space group P2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 55.6, b = 113.7, c = 117.3 Å, α = β = γ = 90.0°. Diffraction data were collected to 2.9 Å resolution using synchrotron radiation at BL24XU of SPring-8.

  19. The Copernicus ultraviolet spectral atlas Tau Scorpii

    NASA Technical Reports Server (NTRS)

    Rogerson, J. B., Jr.; Upson, W. L., II

    1977-01-01

    An ultraviolet spectral atlas was presented for the B0 V star, Tau Scorpii. It was scanned from 949 to 1560 A by the Princeton spectrometer aboard the Copernicus satellite. From 949 to 1420 A the observations have a nominal resolution of 0.05 A. At the longer wavelengths, the resolution was 0.1 A. The atlas was presented in both tables and graphs.

  20. TAU as Tao. [interstellar spacecraft performance

    NASA Technical Reports Server (NTRS)

    Lyman, P. T.; Reid, M. S.

    1989-01-01

    This paper discusses the feasibility of building and launching a truly deep-space spacecraft mission that will penetrate near interstellar space to a depth of one thousand astronomical units (TAU) within a flight time of 50 years. Particular attention is given to the mission profile and to its communications system, power system, and propulsion system. Results of experimental studies indicate that, with advanced technology, reasonable trip times can be achieved and adequate science information can be brought to earth.

  1. Hyperphosphorylation results in tau dysfunction in DNA folding and protection.

    PubMed

    Lu, Yang; He, Hai-Jin; Zhou, Jun; Miao, Jun-Ye; Lu, Jing; He, Ying-Ge; Pan, Rong; Wei, Yan; Liu, Ying; He, Rong-Qiao

    2013-01-01

    Hyperphosphorylation of tau occurs in preclinical and clinical stages of Alzheimer's disease (AD), and hyperphosphorylated tau is the main constituent of the paired helical filaments in the brains of mild cognitive impairment and AD patients. While most of the work described so far focused on the relationship between hyperphosphorylation of tau and microtubule disassembly as well as axonal transport impairments, both phenomena ultimately leading to cell death, little work has been done to study the correlation between tau hyperphosphorylation and DNA damage. As we showed in this study, tau hyperphosphorylation and DNA damage co-occurred under formaldehyde treatment in N2a cells, indicating that phosphorylated tau (p-Tau) induced by formaldehyde may be involved in DNA impairment. After phosphorylation, the effect of tau in preventing DNA from thermal denaturation was diminished, its ability to accelerate DNA renaturation was lost, and its function in protecting DNA from reactive oxygen species (ROS) attack was impaired. Thus, p-Tau is not only associated with the disassembly of the microtubule system, but also plays a crucial role in DNA impairment. Hyperphosphorylation-mediated dysfunction of tau protein in prevention of DNA structure from damage under the attack of ROS may provide novel insights into the mechanisms underlying tauopathies. PMID:24064506

  2. Robust Coefficients Alpha and Omega and Confidence Intervals with Outlying Observations and Missing Data: Methods and Software

    ERIC Educational Resources Information Center

    Zhang, Zhiyong; Yuan, Ke-Hai

    2016-01-01

    Cronbach's coefficient alpha is a widely used reliability measure in social, behavioral, and education sciences. It is reported in nearly every study that involves measuring a construct through multiple items. With non-tau-equivalent items, McDonald's omega has been used as a popular alternative to alpha in the literature. Traditional estimation…

  3. The tau lepton in general relativity

    SciTech Connect

    Nienart, L.

    1988-01-01

    This dissertation presents the results of an investigation into trying to see how the mass of the tau lepton can arise from general Relativistic considerations. The formalism was applied earlier to electrons and predicted both the electron's mass and the muon's mass. The tau leptons mass will be found by considering the contribution of a non-zero magnetic moment to the quaternion fields and the spin affine connection fields in a Riemannian space. The exact mass operator is constructed from these fields, and is then approximated in 3 different ways in order to permit calculation. The expectation value of these approximations to the mass operator is then found, using the relativistic Coulomb wavefunctions. The choice of Coulomb states is due to the consideration that the pairs that comprise the vacuum in this field theory couple to the magnetic moment of the core electron in a manner resembling that of the electrons in the Hydrogen atom. As the coupling the author is considering in his model is that of magnetic dipole by design, an argument is presented in which the Coulombic coupling strength parameters of the Coulomb states are scaled in order to provide a suitable description of the magnetic states which the author is actually interested in. The resulting values for the mass of the tau lepton are then within half an order of magnitude of the experimental values.

  4. Expression of the Escherichia coli K5 capsular antigen: immunoelectron microscopic and biochemical studies with recombinant E. coli.

    PubMed Central

    Kröncke, K D; Boulnois, G; Roberts, I; Bitter-Suermann, D; Golecki, J R; Jann, B; Jann, K

    1990-01-01

    The capsular K5 polysaccharide, a representative of group II capsular antigens of Escherichia coli, has been cloned previously, and three gene regions responsible for polymerization and surface expression have been defined (I. S. Roberts, R. Mountford, R. Hodge, K. B. Jann, and G. J. Boulnois, J. Bacteriol. 170:1305-1310, 1988). In this report, we describe the immunoelectron microscopic analysis of recombinant bacteria expressing the K5 antigen and of mutants defective in either region 1 or region 3 gene functions, as well as the biochemical analysis of the K5 capsular polysaccharide. Whereas the K5 clone expressed the K5 polysaccharide as a well-developed capsule in about 25% of its population, no capsule was observed in whole mount preparations and ultrathin sections of the expression mutants. Immunogold labeling of sections from the region 3 mutant revealed the capsular K5 polysaccharide in the cytoplasm. With the region 1 mutant, the capsular polysaccharide appeared associated with the cell membrane, and, unlike the region 3 mutant polysaccharide, the capsular polysaccharide could be detected in the periplasm after plasmolysis of the bacteria. Polysaccharides were isolated from the homogenized mutants with cetyltrimethylammonium bromide. The polysaccharide from the region 1 mutant had the same size as that isolated from the capsule of the original K5 clone, and both polysaccharides were substituted with phosphatidic acid. The polysaccharide from the region 3 mutant was smaller and was not substituted with phosphatidic acid. These results prompt us to postulate that gene region 3 products are involved in the translocation of the capsular polysaccharide across the cytoplasmic membrane and that region 1 directs the transport of the lipid-substituted capsular polysaccharide through the periplasm and across the outer membrane. Images FIG. 1 FIG. 2 FIG. 3 FIG. 4 FIG. 6 PMID:2404935

  5. Polymeric alkylpyridinium salts permit intracellular delivery of human Tau in rat hippocampal neurons: requirement of Tau phosphorylation for functional deficits.

    PubMed

    Koss, Dave J; Robinson, Lianne; Mietelska-Porowska, Anna; Gasiorowska, Anna; Sepčić, Kristina; Turk, Tom; Jaspars, Marcel; Niewiadomska, Grazyna; Scott, Roderick H; Platt, Bettina; Riedel, Gernot

    2015-12-01

    Patients suffering from tauopathies including frontotemporal dementia (FTD) and Alzheimer's disease (AD) present with intra-neuronal aggregation of microtubule-associated protein Tau. During the disease process, Tau undergoes excessive phosphorylation, dissociates from microtubules and aggregates into insoluble neurofibrillary tangles (NFTs), accumulating in the soma. While many aspects of the disease pathology have been replicated in transgenic mouse models, a region-specific non-transgenic expression model is missing. Complementing existing models, we here report a novel region-specific approach to modelling Tau pathology. Local co-administration of the pore-former polymeric 1,3-alkylpyridinium salts (Poly-APS) extracted from marine sponges, and synthetic full-length 4R recombinant human Tau (hTau) was performed in vitro and in vivo. At low doses, Poly-APS was non-toxic and cultured cells exposed to Poly-APS (0.5 µg/ml) and hTau (1 µg/ml; ~22 µM) had normal input resistance, resting-state membrane potentials and Ca(2+) transients induced either by glutamate or KCl, as did cells exposed to a low concentration of the phosphatase inhibitor Okadaic acid (OA; 1 nM, 24 h). Combined hTau loading and phosphatase inhibition resulted in a collapse of the membrane potential, suppressed excitation and diminished glutamate and KCl-stimulated Ca(2+) transients. Stereotaxic infusions of Poly-APS (0.005 µg/ml) and hTau (1 µg/ml) bilaterally into the dorsal hippocampus at multiple sites resulted in hTau loading of neurons in rats. A separate cohort received an additional 7-day minipump infusion of OA (1.2 nM) intrahippocampally. When tested 2 weeks after surgery, rats treated with Poly-APS+hTau+OA presented with subtle learning deficits, but were also impaired in cognitive flexibility and recall. Hippocampal plasticity recorded from slices ex vivo was diminished in Poly-APS+hTau+OA subjects, but not in other treatment groups. Histological sections confirmed the intracellular

  6. Search for tau- ---> 4pi- 3pi+ (pi0) nu/tau Decays

    SciTech Connect

    Ter-Antonian, R.; Kass, R.; Allmendinger, T.; Hast, C.; /SLAC

    2005-06-21

    A search for the decay of the {tau} lepton to seven charged pions and at most one {pi}{sup 0} was performed using the BABAR detector at the PEP-II e{sup +}e{sup -} collider. The analysis uses data recorded on and near the {Upsilon}(4S) resonance between 1999 and 2003, a total of 124.3 fb{sup -1}. They observe 7 events with an expected background of 11.9 {+-} 2.2 events and calculate a preliminary upper limit of BR({tau}{sup -} {yields} 4{pi}{sup -} 3{pi}{sup +}({pi}{sup 0}){nu}{sub {tau}}) < 2.7 x 10{sup -7} at 90% CL. This is a significant improvement over the previous limit established by the CLEO Collaboration.

  7. The CDF-II tau physics program triggers, tau ID and preliminary results

    SciTech Connect

    C. Pagliarone et al.

    2003-11-03

    The study of processes containing {tau} leptons in the final state will play an important role at Tevatron Run II. Such final states will be relevant both for electroweak studies and measurements as well as in searches for physics beyond the Standard Model. The present paper discusses the physics opportunities and challenges related to the implementation of new set of triggers able to select events containing tau candidates in the final state. They illustrate, in particular, the physics capabilities for a variety of new physics scenarios such as supersymmetry (SUSY), SUSY with Rp-parity violation, with Bilinear parity violation or models with the violation of lepton flavor. Finally, they present the first Run II results obtained using some of the described tau triggers.

  8. Observation of CO2 in Comet C/2012 K5 LINEAR

    NASA Astrophysics Data System (ADS)

    McKay, Adam; Kelley, Michael; DiSanti, Michael; Chanover, Nancy

    2012-12-01

    The study of cometary composition is important to understanding the formation and evolution of our solar system. Comets have undergone very little thermal evolution in their lifetimes, which results in their near pristine composition. The nucleus of a comet is very rarely detected directly. Instead, we observe the coma that surrounds the nucleus. Physical and chemical processes in the coma affect its composition, and therefore coma composition is not a direct representation of nuclear composition. An important trend is the observed variation of coma composition with heliocentric distance, most likely influenced by the volatility of the main surface ices, H2O, CO2, and CO. Infrared studies of these molecules are complicated by telluric features, so often daughter molecules of these species such as OH are observed instead. A potentially effective tracer for these primary ices is atomic oxygen in the coma. However, the relationship between these ices and atomic oxygen is only understood at a qualitative level. We propose to use Spitzer observations in IRAC's 4.5 micron band pass to observe the CO2 v3 band at 4.26 microns in comet C/2012 K5 LINEAR. These observations will be coordinated with observations of atomic oxygen obtained at Apache Point Observatory and observations of H2O at Keck. These near simultaneous observations of H2O, CO2, and atomic oxygen in a cometary coma will increase our understanding of the link between these primary ices and atomic oxygen. With a complete understanding of the relationship between atomic oxygen and the primary ices on the nucleus, observations of atomic oxygen can serve as a powerful proxy for the production of these primary volatiles and aid our understanding of the variation in coma composition as a function of heliocentric distance, and therefore the composition of the nucleus and how our solar system was formed.

  9. Survivability of Psychrobacter cryohalolentis K5 Under Simulated Martian Surface Conditions

    NASA Astrophysics Data System (ADS)

    Smith, David J.; Schuerger, Andrew C.; Davidson, Mark M.; Pacala, Stephen W.; Bakermans, Corien; Onstott, Tullis C.

    2009-03-01

    Spacecraft launched to Mars can retain viable terrestrial microorganisms on board that may survive the interplanetary transit. Such biota might compromise the search for life beyond Earth if capable of propagating on Mars. The current study explored the survivability of Psychrobacter cryohalolentis K5, a psychrotolerant microorganism obtained from a Siberian permafrost cryopeg, under simulated martian surface conditions of high ultraviolet irradiation, high desiccation, low temperature, and low atmospheric pressure. First, a desiccation experiment compared the survival of P. cryohalolentis cells embedded, or not embedded, within a medium/salt matrix (MSM) maintained at 25°C for 24 h within a laminar flow hood. Results indicate that the presence of the MSM enhanced survival of the bacterial cells by 1 to 3 orders of magnitude. Second, tests were conducted in a Mars Simulation Chamber to determine the UV tolerance of the microorganism. No viable vegetative cells of P. cryohalolentis were detected after 8 h of exposure to Mars-normal conditions of 4.55 W/m2 UVC irradiation (200-280 nm), -12.5°C, 7.1 mbar, and a Mars gas mix composed of CO2 (95.3%), N2 (2.7%), Ar (1.6%), O2 (0.2%), and H2O (0.03%). Third, an experiment was conducted within the Mars chamber in which total atmospheric opacities were simulated at τ = 0.1 (dust-free CO2 atmosphere at 7.1 mbar), 0.5 (normal clear sky with 0.4 = dust opacity and 0.1 = CO2-only opacity), and 3.5 (global dust storm) to determine the survivability of P. cryohalolentis to partially shielded UVC radiation. The survivability of the bacterium increased with the level of UVC attenuation, though population levels still declined several orders of magnitude compared to UVC-absent controls over an 8 h exposure period.

  10. PET Imaging of Tau Deposition in the Aging Human Brain.

    PubMed

    Schöll, Michael; Lockhart, Samuel N; Schonhaut, Daniel R; O'Neil, James P; Janabi, Mustafa; Ossenkoppele, Rik; Baker, Suzanne L; Vogel, Jacob W; Faria, Jamie; Schwimmer, Henry D; Rabinovici, Gil D; Jagust, William J

    2016-03-01

    Tau pathology is a hallmark of Alzheimer's disease (AD) but also occurs in normal cognitive aging. Using the tau PET agent (18)F-AV-1451, we examined retention patterns in cognitively normal older people in relation to young controls and AD patients. Age and β-amyloid (measured using PiB PET) were differentially associated with tau tracer retention in healthy aging. Older age was related to increased tracer retention in regions of the medial temporal lobe, which predicted worse episodic memory performance. PET detection of tau in other isocortical regions required the presence of cortical β-amyloid and was associated with decline in global cognition. Furthermore, patterns of tracer retention corresponded well with Braak staging of neurofibrillary tau pathology. The present study defined patterns of tau tracer retention in normal aging in relation to age, cognition, and β-amyloid deposition. PMID:26938442

  11. Tau protein is essential for stress-induced brain pathology.

    PubMed

    Lopes, Sofia; Vaz-Silva, João; Pinto, Vitor; Dalla, Christina; Kokras, Nikolaos; Bedenk, Benedikt; Mack, Natalie; Czisch, Michael; Almeida, Osborne F X; Sousa, Nuno; Sotiropoulos, Ioannis

    2016-06-28

    Exposure to chronic stress is frequently accompanied by cognitive and affective disorders in association with neurostructural adaptations. Chronic stress was previously shown to trigger Alzheimer's-like neuropathology, which is characterized by Tau hyperphosphorylation and missorting into dendritic spines followed by memory deficits. Here, we demonstrate that stress-driven hippocampal deficits in wild-type mice are accompanied by synaptic missorting of Tau and enhanced Fyn/GluN2B-driven synaptic signaling. In contrast, mice lacking Tau [Tau knockout (Tau-KO) mice] do not exhibit stress-induced pathological behaviors and atrophy of hippocampal dendrites or deficits of hippocampal connectivity. These findings implicate Tau as an essential mediator of the adverse effects of stress on brain structure and function. PMID:27274066

  12. Wess-Zumino current and the structure of the decay tau- -->K- pi- K+ nu tau.

    PubMed

    Coan, T E; Gao, Y S; Liu, F; Stroynowski, R; Artuso, M; Boulahouache, C; Blusk, S; Butt, J; Dambasuren, E; Dorjkhaidav, O; Haynes, J; Menaa, N; Mountain, R; Muramatsu, H; Nandakumar, R; Redjimi, R; Sia, R; Skwarnicki, T; Stone, S; Wang, J C; Zhang, Kevin; Mahmood, A H; Csorna, S E; Bonvicini, G; Cinabro, D; Dubrovin, M; Bornheim, A; Lipeles, E; Pappas, S P; Shapiro, A; Weinstein, A J; Briere, R A; Chen, G P; Ferguson, T; Tatishvili, G; Vogel, H; Watkins, M E; Adam, N E; Alexander, J P; Berkelman, K; Boisvert, V; Cassel, D G; Duboscq, J E; Ecklund, K M; Ehrlich, R; Galik, R S; Gibbons, L; Gittelman, B; Gray, S W; Hartill, D L; Heltsley, B K; Hsu, L; Jones, C D; Kandaswamy, J; Kreinick, D L; Kuznetsov, V E; Magerkurth, A; Mahlke-Krüger, H; Meyer, T O; Patterson, J R; Pedlar, T K; Peterson, D; Pivarski, J; Riley, D; Sadoff, A J; Schwarthoff, H; Shepherd, M R; Sun, W M; Thayer, J G; Urner, D; Wilksen, T; Weinberger, M; Athar, S B; Avery, P; Breva-Newell, L; Potlia, V; Stoeck, H; Yelton, J; Eisenstein, B I; Gollin, G D; Karliner, I; Lowrey, N; Naik, P; Sedlack, C; Selen, M; Thaler, J J; Williams, J; Edwards, K W; Besson, D; Gao, K Y; Gong, D T; Kubota, Y; Li, S Z; Poling, R; Scott, A W; Smith, A; Stepaniak, C J; Urheim, J; Metreveli, Z; Seth, K K; Tomaradze, A; Zweber, P; Arms, K; Eckhart, E; Gan, K K; Gwon, C; Severini, H; Skubic, P; Asner, D M; Dytman, S A; Mehrabyan, S; Mueller, J A; Nam, S; Savinov, V; Huang, G S; Miller, D H; Pavlunin, V; Sanghi, B; Shibata, E I; Shipsey, I P J; Adams, G S; Chasse, M; Cummings, J P; Danko, I; Napolitano, J; Cronin-Hennessy, D; Park, C S; Park, W; Thayer, J B; Thorndike, E H

    2004-06-11

    We present the first study of the vector (Wess-Zumino) current in tau(-)-->K-pi-K+nu(tau) decay using data collected with the CLEO III detector at the Cornell Electron Storage Ring. We determine the quantitative contributions to the decay width from the vector and axial vector currents. Within the framework of a model by Kühn and Mirkes, we identify the quantitative contributions to the total decay rate from the intermediate states omegapi, rho(')pi, and K*K. PMID:15245150

  13. Resonance Effective Theory Approach to {tau} {yields} 3{pi}{nu}{tau} Decays

    SciTech Connect

    Gomez Dumm, D.; Pich, A.; Portoles, J.

    2004-12-02

    The decays {tau} {yields} 3{pi}{nu}{tau} are analyzed in the framework of the resonance effective theory of QCD, We derive the effective chiral Lagrangian relevant for the evaluation of the hadronic axial-vector current, taking into account the constraints imposed by QCD on the high energy asymptotic behaviour. Then we fit the unknown parameters to the spectral function and branching ratio measured by ALEPH, showing that the theory is in good agreement with experimental data. A detailed description of the work sketched here can be found.

  14. Temperature and toxic Tau in Alzheimer's disease: new insights

    PubMed Central

    Carrettiero, Daniel Carneiro; Santiago, Fernando Enrique; Motzko-Soares, Anna Carolina Parracho; Almeida, Maria Camila

    2015-01-01

    Alzheimer's disease (AD), the most common dementia in the elderly, is characterized by cognitive impairment and severe autonomic symptoms such as disturbance in core body temperature (Tc), which may be predictors or early events in AD onset. Inclusions of phosphorylated Tau (p-Tau) are a hallmark of AD and other neurodegenerative disorders called “Tauopathies.” Animal and human studies show that anesthesia augments p-Tau levels through reduction of Tc, with implications for AD. Additionally, hypothermia impairs memory and cognitive function. The molecular networks related to Tc that are associated with AD remain poorly characterized. Under physiological conditions, Tau binds microtubules, promoting their assembly and stability. The dynamically regulated Tau-microtubule interaction plays an important role in structural remodeling of the cytoskeleton, having important functions in neuronal plasticity and memory in the hippocampus. Hypothermia-induced increases in p-Tau levels are significant, with an 80% increase for each degree Celsius below normothermic conditions. Although the effects of temperature on Tau phosphorylation are evident, its effects on p-Tau degradation remain poorly understoodWe review information concerning the mechanisms of Tau regulation of neuron plasticity via its effects on microtubule dynamics, with focus on pathways regulating the abundance of phosphorylated Tau species.  We highlight the effects of temperature on molecular mechanisms influencing the development of Tau-related diseases. Specifically, we argue that cold might preferentially affects central nervous system structures that are highly reliant upon plasticity, such as the hippocampus, and that the effect of cold on Tau phosphorylation may constitute a pathology-initiating trigger leading to neurodegeneration. PMID:27227069

  15. Tau: The Center of a Signaling Nexus in Alzheimer's Disease

    PubMed Central

    Khan, Shahzad S.; Bloom, George S.

    2016-01-01

    Tau is a microtubule-associated protein whose misfolding, hyper-phosphorylation, loss of normal function and toxic gain of function are linked to several neurodegenerative disorders, including Alzheimer's disease (AD). This review discusses the role of tau in amyloid-β (Aβ) induced toxicity in AD. The consequences of tau dysfunction, starting from the axon and concluding at somadendritic compartments, will be highlighted. PMID:26903798

  16. Waring's problem with the Ramanujan \\tau-function

    NASA Astrophysics Data System (ADS)

    Garaev, M. Z.; Garcia, V. C.; Konyagin, S. V.

    2008-02-01

    We prove that for every integer N the Diophantine equation \\sum_{i=1}^{74000}\\tau(n_i)=N, where \\tau(n) is the Ramanujan \\tau-function, has a solution in positive integers n_1, n_2,\\dots, n_{74000} satisfying the condition \\max_{1\\le i\\le 74000}n_i\\,{\\ll}\\vert N\\vert^{2/11}+1. We also consider similar questions in residue fields modulo a large prime p.

  17. MSUT2 is a determinant of susceptibility to tau neurotoxicity.

    PubMed

    Guthrie, Chris R; Greenup, Lynne; Leverenz, James B; Kraemer, Brian C

    2011-05-15

    Lesions containing abnormal aggregated tau protein are one of the diagnostic hallmarks of Alzheimer's disease (AD) and related tauopathy disorders. How aggregated tau leads to dementia remains enigmatic, although neuronal dysfunction and loss clearly contribute. We previously identified sut-2 as a gene required for tau neurotoxicity in a transgenic Caenorhabditis elegans model of tauopathy. Here, we further explore the role of sut-2 and show that overexpression of SUT-2 protein enhances tau-induced neuronal dysfunction, neurotoxicity and accumulation of insoluble tau. We also explore the relationship between sut-2 and its human homolog, mammalian SUT-2 (MSUT2) and find both proteins to be predominantly nuclear and localized to SC35-positive nuclear speckles. Using a cell culture model for the accumulation of pathological tau, we find that high tau levels lead to increased expression of MSUT2 protein. We analyzed MSUT2 protein in age-matched post-mortem brain samples from AD patients and observe a marked decrease in overall MSUT2 levels in the temporal lobe of AD patients. Analysis of post-mortem tissue from AD cases shows a clear reduction in neuronal MSUT2 levels in brain regions affected by tau pathology, but little change in regions lacking tau pathology. RNAi knockdown of MSUT2 in cultured human cells overexpressing tau causes a marked decrease in tau aggregation. Both cell culture and post-mortem tissue studies suggest that MSUT2 levels may influence neuronal vulnerability to tau toxicity and aggregation. Thus, neuroprotective strategies targeting MSUT2 may be of therapeutic interest for tauopathy disorders. PMID:21355046

  18. MSUT2 is a determinant of susceptibility to tau neurotoxicity

    PubMed Central

    Guthrie, Chris R.; Greenup, Lynne; Leverenz, James B.; Kraemer, Brian C.

    2011-01-01

    Lesions containing abnormal aggregated tau protein are one of the diagnostic hallmarks of Alzheimer's disease (AD) and related tauopathy disorders. How aggregated tau leads to dementia remains enigmatic, although neuronal dysfunction and loss clearly contribute. We previously identified sut-2 as a gene required for tau neurotoxicity in a transgenic Caenorhabditis elegans model of tauopathy. Here, we further explore the role of sut-2 and show that overexpression of SUT-2 protein enhances tau-induced neuronal dysfunction, neurotoxicity and accumulation of insoluble tau. We also explore the relationship between sut-2 and its human homolog, mammalian SUT-2 (MSUT2) and find both proteins to be predominantly nuclear and localized to SC35-positive nuclear speckles. Using a cell culture model for the accumulation of pathological tau, we find that high tau levels lead to increased expression of MSUT2 protein. We analyzed MSUT2 protein in age-matched post-mortem brain samples from AD patients and observe a marked decrease in overall MSUT2 levels in the temporal lobe of AD patients. Analysis of post-mortem tissue from AD cases shows a clear reduction in neuronal MSUT2 levels in brain regions affected by tau pathology, but little change in regions lacking tau pathology. RNAi knockdown of MSUT2 in cultured human cells overexpressing tau causes a marked decrease in tau aggregation. Both cell culture and post-mortem tissue studies suggest that MSUT2 levels may influence neuronal vulnerability to tau toxicity and aggregation. Thus, neuroprotective strategies targeting MSUT2 may be of therapeutic interest for tauopathy disorders. PMID:21355046

  19. Cellular factors modulating the mechanism of tau protein aggregation.

    PubMed

    Fontaine, Sarah N; Sabbagh, Jonathan J; Baker, Jeremy; Martinez-Licha, Carlos R; Darling, April; Dickey, Chad A

    2015-05-01

    Pathological accumulation of the microtubule-associated protein tau, in the form of neurofibrillary tangles, is a major hallmark of Alzheimer's disease, the most prevalent neurodegenerative condition worldwide. In addition to Alzheimer's disease, a number of neurodegenerative diseases, called tauopathies, are characterized by the accumulation of aggregated tau in a variety of brain regions. While tau normally plays an important role in stabilizing the microtubule network of the cytoskeleton, its dissociation from microtubules and eventual aggregation into pathological deposits is an area of intense focus for therapeutic development. Here we discuss the known cellular factors that affect tau aggregation, from post-translational modifications to molecular chaperones. PMID:25666877

  20. Tau Mislocation in Glucocorticoid-Triggered Hippocampal Pathology.

    PubMed

    Pinheiro, Sara; Silva, Joana; Mota, Cristina; Vaz-Silva, João; Veloso, Ana; Pinto, Vítor; Sousa, Nuno; Cerqueira, João; Sotiropoulos, Ioannis

    2016-09-01

    The exposure to high glucocorticoids (GC) triggers neuronal atrophy and cognitive deficits, but the exact cellular mechanisms underlying the GC-associated dendritic remodeling and spine loss are still poorly understood. Previous studies have implicated sustained GC elevations in neurodegenerative mechanisms through GC-evoked hyperphosphorylation of the cytoskeletal protein Tau while Tau mislocation has recently been proposed as relevant in Alzheimer's disease (AD) pathology. In light of the dual cytoplasmic and synaptic role of Tau, this study monitored the impact of prolonged GC treatment on Tau intracellular localization and its phosphorylation status in different cellular compartments. We demonstrate, both by biochemical and ultrastructural analysis, that GC administration led to cytosolic and dendritic Tau accumulation in rat hippocampus, and triggered Tau hyperphosphorylation in epitopes related to its malfunction (Ser396/404) and cytoskeletal pathology (e.g., Thr231 and Ser262). In addition, we show, for the first time, that chronic GC administration also increased Tau levels in synaptic compartment; however, at the synapse, there was an increase in phosphorylation of Ser396/404, but a decrease of Thr231. These GC-triggered Tau changes were paralleled by reduced levels of synaptic scaffolding proteins such as PSD-95 and Shank proteins as well as reduced dendritic branching and spine loss. These in vivo findings add to our limited knowledge about the underlying mechanisms of GC-evoked synaptic atrophy and neuronal disconnection implicating Tau missorting in mechanism(s) of synaptic damage, beyond AD pathology. PMID:26328538

  1. Updated measurement of the tau lifetime at SLD

    SciTech Connect

    1996-07-23

    We present an updated measurement of the tau lifetime at SLD. 4316 {tau}-pair events, selected from a 150k Z{sup 0} data sample, are analyzed using three techniques: decay length, impact parameter, and impact parameter difference methods. The measurement benefits from the small and stable interaction region at the SLC and the precision CCD pixel vertex detector of the SLD. The combined result is: {tau}{sub {tau}} = 288.1 {+-} 6.1(stat) {+-} 3.3(syst) fs.

  2. Tau physiology and pathomechanisms in frontotemporal lobar degeneration.

    PubMed

    Bodea, Liviu-Gabriel; Eckert, Anne; Ittner, Lars Matthias; Piguet, Olivier; Götz, Jürgen

    2016-08-01

    Frontotemporal lobar degeneration (FTLD) has been associated with toxic intracellular aggregates of hyperphosphorylated tau (FTLD-tau). Moreover, genetic studies identified mutations in the MAPT gene encoding tau in familial cases of the disease. In this review, we cover a range of aspects of tau function, both in the healthy and diseased brain, discussing several in vitro and in vivo models. Tau structure and function in the healthy brain is presented, accentuating its distinct compartmentalization in neurons and its role in microtubule stabilization and axonal transport. Furthermore, tau-driven pathology is discussed, introducing current concepts and the underlying experimental evidence. Different aspects of pathological tau phosphorylation, the protein's genomic and domain organization as well as its spreading in disease, together with MAPT-associated mutations and their respective models are presented. Dysfunction related to other post-transcriptional modifications and their effect on normal neuronal functions such as cell cycle, epigenetics and synapse dynamics are also discussed, providing a mechanistic explanation for the observations made in FTLD-tau cases, with the possibility for therapeutic intervention. In this review, we cover aspects of tau function, both in the healthy and diseased brain, referring to different in vitro and in vivo models. In healthy neurons, tau is compartmentalized, with higher concentrations found in the distal part of the axon. Cargo molecules are sensitive to this gradient. A disturbed tau distribution, as found in frontotemporal lobar degeneration (FTLD-tau), has severe consequences for cellular physiology: tau accumulates in the neuronal soma and dendrites, leading among others to microtubule depolymerization and impaired axonal transport. Tau forms insoluble aggregates that sequester additional molecules stalling cellular physiology. Neuronal communication is gradually lost as toxic tau accumulates in dendritic spines

  3. Cellular factors modulating the mechanism of tau protein aggregation

    PubMed Central

    Fontaine, Sarah N.; Sabbagh, Jonathan J.; Baker, Jeremy; Martinez-Licha, Carlos R.; Darling, April

    2015-01-01

    Pathological accumulation of the microtubule-associated protein tau, in the form of neurofibrillary tangles, is a major hallmark of Alzheimer’s disease, the most prevalent neurodegenerative condition worldwide. In addition to Alzheimer’s disease, a number of neurodegenerative diseases, called tauopathies, are characterized by the accumulation of aggregated tau in a variety of brain regions. While tau normally plays an important role in stabilizing the microtubule network of the cytoskeleton, its dissociation from microtubules and eventual aggregation into pathological deposits is an area of intense focus for therapeutic development. Here we discuss the known cellular factors that affect tau aggregation, from post-translational modifications to molecular chaperones. PMID:25666877

  4. Nuclear Tau and Its Potential Role in Alzheimer's Disease.

    PubMed

    Bukar Maina, Mahmoud; Al-Hilaly, Youssra K; Serpell, Louise C

    2016-01-01

    Tau protein, found in both neuronal and non-neuronal cells, forms aggregates in neurons that constitutes one of the hallmarks of Alzheimer's disease (AD). For nearly four decades, research efforts have focused more on tau's role in physiology and pathology in the context of the microtubules, even though, for over three decades, tau has been localised in the nucleus and the nucleolus. Its nuclear and nucleolar localisation had stimulated many questions regarding its role in these compartments. Data from cell culture, mouse brain, and the human brain suggests that nuclear tau could be essential for genome defense against cellular distress. However, its nature of translocation to the nucleus, its nuclear conformation and interaction with the DNA and other nuclear proteins highly suggest it could play multiple roles in the nucleus. To find efficient tau-based therapies, there is a need to understand more about the functional relevance of the varied cellular distribution of tau, identify whether specific tau transcripts or isoforms could predict tau's localisation and function and how they are altered in diseases like AD. Here, we explore the cellular distribution of tau, its nuclear localisation and function and its possible involvement in neurodegeneration. PMID:26751496

  5. NMR Meets Tau: Insights into Its Function and Pathology.

    PubMed

    Lippens, Guy; Landrieu, Isabelle; Smet, Caroline; Huvent, Isabelle; Gandhi, Neha S; Gigant, Benoît; Despres, Clément; Qi, Haoling; Lopez, Juan

    2016-01-01

    In this review, we focus on what we have learned from Nuclear Magnetic Resonance (NMR) studies on the neuronal microtubule-associated protein Tau. We consider both the mechanistic details of Tau: the tubulin relationship and its aggregation process. Phosphorylation of Tau is intimately linked to both aspects. NMR spectroscopy has depicted accurate phosphorylation patterns by different kinases, and its non-destructive character has allowed functional assays with the same samples. Finally, we will discuss other post-translational modifications of Tau and its interaction with other cellular factors in relationship to its (dys)function. PMID:27338491

  6. Connecting the Dots Between Tau Dysfunction and Neurodegeneration

    PubMed Central

    Frost, Bess; Götz, Jürgen; Feany, Mel B.

    2014-01-01

    Tauopathies are devastating and ultimately fatal neurodegenerative diseases, which are histopathologically defined by insoluble filamentous deposits of abnormally phosphorylated tau protein within neurons and glia. Identifying the causes of abnormal tau phosphorylation and subsequent aggregation has been the focus of much research, and is currently a major target for the development of therapeutic interventions for tauopathies, including Alzheimer’s disease. Recently much has been learned about the sequence of events that lead from tau dysfunction to neuronal death. This review focuses on the cascade of events that are catalyzed by pathological tau, and highlights current and potential therapeutic strategies to target this pathway. PMID:25172552

  7. NMR Meets Tau: Insights into Its Function and Pathology

    PubMed Central

    Lippens, Guy; Landrieu, Isabelle; Smet, Caroline; Huvent, Isabelle; Gandhi, Neha S.; Gigant, Benoît; Despres, Clément; Qi, Haoling; Lopez, Juan

    2016-01-01

    In this review, we focus on what we have learned from Nuclear Magnetic Resonance (NMR) studies on the neuronal microtubule-associated protein Tau. We consider both the mechanistic details of Tau: the tubulin relationship and its aggregation process. Phosphorylation of Tau is intimately linked to both aspects. NMR spectroscopy has depicted accurate phosphorylation patterns by different kinases, and its non-destructive character has allowed functional assays with the same samples. Finally, we will discuss other post-translational modifications of Tau and its interaction with other cellular factors in relationship to its (dys)function. PMID:27338491

  8. Final report on the key comparison CCPR-K5: Spectral diffuse reflectance

    NASA Astrophysics Data System (ADS)

    Nadal, Maria; Eckerle, Kenneth L.; Early, Edward A.; Ohno, Yoshi

    2013-01-01

    The CCPR K5 key comparison on spectral diffuse reflectance was carried out in the framework of the CIPM Mutual Recognition Arrangement, by 13 national metrology institutes (MMIs) as participants. The participants were CSIR-NML (South Africa), HUT (Finland), IFA-CSIC (Spain), KRISS (Republic of Korea), MSL (New Zealand), NIM (China), NIST (United States of America), NMIJ (Japan), NPL (United Kingdom), NRC (Canada), OMH (Hungary), PTB (Germany) and VNIIOFI (Russia Federation). NIST (USA) piloted the comparison. The aim of this comparison was to check the agreement of measurement of the spectral diffuse reflectance among participants, using the measurement geometry of d/0 or 0/d in the wavelength range of 360 nm to 820 nm at 20 nm increment. The comparison was a star type comparison with the samples provided by the pilot laboratory and with the measurement sequence: Pilot-Participant-Pilot. Spectralon and matte white ceramic tiles were used as the transfer standards. Each participant received three of each type of sample and at least one sample of each type was measured three times on three separate days, and the other two samples were measured once. The report presents the description of the measurement facilities, procedures and uncertainties of all the participants as well as the results of the comparison. Measurement results from the participants and their associated uncertainties were analyzed in accordance with the Guidelines for CCPR Key Comparison Report Preparation, using weighted mean with cut-off. For the calculation of the Key Comparison Reference Value (KCRV), as agreed by the participants, the data of both samples were used for the 460 nm to 820 nm region and only the data of the Spectralon samples were used in the spectral region of 360 nm to 440 nm. The unilateral degrees of equivalence (DoE) calculated for each participant are mostly consistent within the uncertainty (k = 2) of the DoE. This international comparison of spectral diffuse reflectance

  9. Proceedings, High-Precision $\\alpha_s$ Measurements from LHC to FCC-ee

    SciTech Connect

    d'Enterria, David; Skands, Peter Z.

    2015-01-01

    This document provides a writeup of all contributions to the workshop on "High precision measurements of $\\alpha_s$: From LHC to FCC-ee" held at CERN, Oct. 12--13, 2015. The workshop explored in depth the latest developments on the determination of the QCD coupling $\\alpha_s$ from 15 methods where high precision measurements are (or will be) available. Those include low-energy observables: (i) lattice QCD, (ii) pion decay factor, (iii) quarkonia and (iv) $\\tau$ decays, (v) soft parton-to-hadron fragmentation functions, as well as high-energy observables: (vi) global fits of parton distribution functions, (vii) hard parton-to-hadron fragmentation functions, (viii) jets in $e^\\pm$p DIS and $\\gamma$-p photoproduction, (ix) photon structure function in $\\gamma$-$\\gamma$, (x) event shapes and (xi) jet cross sections in $e^+e^-$ collisions, (xii) W boson and (xiii) Z boson decays, and (xiv) jets and (xv) top-quark cross sections in proton-(anti)proton collisions. The current status of the theoretical and experimental uncertainties associated to each extraction method, the improvements expected from LHC data in the coming years, and future perspectives achievable in $e^+e^-$ collisions at the Future Circular Collider (FCC-ee) with $\\cal{O}$(1--100 ab$^{-1}$) integrated luminosities yielding 10$^{12}$ Z bosons and jets, and 10$^{8}$ W bosons and $\\tau$ leptons, are thoroughly reviewed. The current uncertainty of the (preliminary) 2015 strong coupling world-average value, $\\alpha_s(m_Z)$ = 0.1177 $\\pm$ 0.0013, is about 1\\%. Some participants believed this may be reduced by a factor of three in the near future by including novel high-precision observables, although this opinion was not universally shared. At the FCC-ee facility, a factor of ten reduction in the $\\alpha_s$ uncertainty should be possible, mostly thanks to the huge Z and W data samples available.

  10. Stabilization of Microtubule-Unbound Tau via Tau Phosphorylation at Ser262/356 by Par-1/MARK Contributes to Augmentation of AD-Related Phosphorylation and Aβ42-Induced Tau Toxicity

    PubMed Central

    Ando, Kanae; Maruko-Otake, Akiko; Ohtake, Yosuke; Hayashishita, Motoki; Sekiya, Michiko; Iijima, Koichi M.

    2016-01-01

    Abnormal accumulation of the microtubule-interacting protein tau is associated with neurodegenerative diseases including Alzheimer’s disease (AD). β-amyloid (Aβ) lies upstream of abnormal tau behavior, including detachment from microtubules, phosphorylation at several disease-specific sites, and self-aggregation into toxic tau species in AD brains. To prevent the cascade of events leading to neurodegeneration in AD, it is essential to elucidate the mechanisms underlying the initial events of tau mismetabolism. Currently, however, these mechanisms remain unclear. In this study, using transgenic Drosophila co-expressing human tau and Aβ, we found that tau phosphorylation at AD-related Ser262/356 stabilized microtubule-unbound tau in the early phase of tau mismetabolism, leading to neurodegeneration. Aβ increased the level of tau detached from microtubules, independent of the phosphorylation status at GSK3-targeted SP/TP sites. Such mislocalized tau proteins, especially the less phosphorylated species, were stabilized by phosphorylation at Ser262/356 via PAR-1/MARK. Levels of Ser262 phosphorylation were increased by Aβ42, and blocking this stabilization of tau suppressed Aβ42-mediated augmentation of tau toxicity and an increase in the levels of tau phosphorylation at the SP/TP site Thr231, suggesting that this process may be involved in AD pathogenesis. In contrast to PAR-1/MARK, blocking tau phosphorylation at SP/TP sites by knockdown of Sgg/GSK3 did not reduce tau levels, suppress tau mislocalization to the cytosol, or diminish Aβ-mediated augmentation of tau toxicity. These results suggest that stabilization of microtubule-unbound tau by phosphorylation at Ser262/356 via the PAR-1/MARK may act in the initial steps of tau mismetabolism in AD pathogenesis, and that such tau species may represent a potential therapeutic target for AD. PMID:27023670