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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. Alpha1-antichymotrypsin, an inflammatory protein overexpressed in Alzheimer's disease brain, induces tau phosphorylation in neurons.

    PubMed

    Padmanabhan, Jaya; Levy, Monique; Dickson, Dennis W; Potter, Huntington

    2006-11-01

    Amyloid plaques and neurofibrillary tangles are key pathological features of Alzheimer's disease. Alzheimer's disease pathology is also characterized by neuroinflammation and neuronal degeneration, with the proteins associated with inflammatory responses being found in tight association with the plaques. One such protein is the serine protease inhibitor alpha-1-antichymotrypsin (ACT). ACT has been shown to promote Abeta polymerization in vitro and in vivo, and levels of ACT protein in plasma and cerebrospinal fluid from Alzheimer's patients have been found to correlate with progression of dementia. Here we investigated the possible involvement of ACT in tau phosphorylation and tangle formation. As was previously found for Alzheimer's disease, brains from patients with non-Alzheimer's tauopathies exhibited an enhanced expression of ACT, which correlated with the level of tau hyperphosphorylation. Transgenic mice expressing human ACT alone or ACT along with mutant human amyloid precursor protein (APP) showed a significant increase in tau phosphorylation, suggesting that this inflammatory protein can induce tau hyperphosphorylation. The increase in phosphorylation was observed at PHF-1 (P-Ser396/P-Thr404), P-Ser202 and P-Thr231 sites on tau, the P-tau epitopes that are associated with tangles in the patients. This result was further confirmed by the finding that addition of purified ACT induced the same Alzheimer's disease-related tau hyperphosphorylation in cortical neurons cultured in vitro. This correlated with an increase in extracellular signal regulated kinase (ERK) and glycogen synthase kinase-3 activation, indicating their involvement in ACT-induced tau phosphorylation. The ACT-treated neurons showed neurite loss and subsequently underwent apoptosis. Approximately 40-50% of neurons were TUNEL positive by 6 and at 24 h >70% of the neurons showed staining suggesting that ACT was inducing apoptosis in these neurons. These findings indicate that inappropriate

  8. Estrogen dissociates Tau and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor subunit in postischemic hippocampus.

    PubMed

    Cardona-Gómez, Gloria Patricia; Arango-Davila, Cesar; Gallego-Gómez, Juan Carlos; Barrera-Ocampo, Alvaro; Pimienta, Hernan; Garcia-Segura, Luis Miguel

    2006-08-21

    During cerebral ischemia, part of the damage associated with the hyperactivation of glutamate receptors results from the hyperphosphorylation of the microtubule-associated protein Tau. Previous studies have shown that estradiol treatment reduces neural damage after cerebral ischemia. Here, we show that transient occlusion of the middle cerebral artery results in the hyperphosphorylation of Tau and in a significant increase in the association of Tau with glycogen synthase kinase-3beta and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid type glutamate receptor subunits 2/3 in the hippocampus. Estradiol treatment decreased hippocampal injury, inhibited glycogen synthase kinase-3beta and decreased the hyperphosphorylation of Tau and the interaction of Tau with glycogen synthase kinase-3beta and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor. These findings suggest that ischemia produces a strong association between Tau and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor, and estradiol can exert at least part of its neuroprotective activity through inhibition of glycogen synthase kinase-3beta.

  9. More than just two peas in a pod: common amyloidogenic properties of tau and alpha-synuclein in neurodegenerative diseases.

    PubMed

    Lee, Virginia M-Y; Giasson, Benoit I; Trojanowski, John Q

    2004-03-01

    Intracytoplasmic filamentous aggregates, such as neurofibrillary tangles in Alzheimer's disease and Lewy bodies in Parkinson's disease, are composed of the proteins tau and alpha-synuclein, respectively. These pathological inclusions are linked directly to the etiology and mechanisms of disease in a wide spectrum of neurodegenerative disorders, termed 'tauopathies' and 'synucleinopathies'. Emerging evidence indicates that there is frequent overlap of the pathological and clinical features of patients with tauopathies and synucleinopathies, thereby re-enforcing the notion that these disorders might be linked mechanistically. Indeed, several lines of investigation suggest that tau and alpha-synuclein might constitute a unique class of unstructured proteins that assemble predominantly into homopolymeric (rather than heteropolymeric) fibrils, which deposit mainly in separate amyloid inclusions, but occasionally deposit together. Thus, the ability of tau and alpha-synuclein to affect each other directly or indirectly might contribute to the overlap in the clinical and pathological features of tauopathies and synucleinopathies.

  10. Spectral irradiance calibration in the infrared. II - Alpha Tau and the recalibration of the IRAS low resolution spectrometer

    NASA Technical Reports Server (NTRS)

    Cohen, Martin; Walker, Russell G.; Witteborn, Fred C.

    1992-01-01

    A general process for creating complete, continuous, and absolutely calibrated 1-35 micron stellar spectra is described. The method is demonstrated by constructing an absolutely calibrated 1-35 micron spectrum of Alpha Tau and the method is independently validated using new observations. The absolute calibration of the IRAS low resolution spectrometer (LRS) data base is investigated by comparing the observed spectrum of Alpha Tau with that assumed in the original LRS calibration scheme. An analysis of asteroidal LRS spectra results in an independent assessment of the calibration problems with the LRS and provides a natural complement to the effort based on Alpha Tau. A direct comparison of LRS stellar spectra with independently calibrated long-wavelength airborne and ground-based spectra is made.

  11. AlphaScreen HTS and live-cell bioluminescence resonance energy transfer (BRET) assays for identification of Tau-Fyn SH3 interaction inhibitors for Alzheimer disease.

    PubMed

    Cochran, J Nicholas; Diggs, Pauleatha V; Nebane, N Miranda; Rasmussen, Lynn; White, E Lucile; Bostwick, Robert; Maddry, Joseph A; Suto, Mark J; Roberson, Erik D

    2014-12-01

    Alzheimer disease (AD) is the most common neurodegenerative disease, and with Americans' increasing longevity, it is becoming an epidemic. There are currently no effective treatments for this disorder. Abnormalities of Tau track more closely with cognitive decline than the most studied therapeutic target in AD, amyloid-β, but the optimal strategy for targeting Tau has not yet been identified. On the basis of considerable preclinical data from AD models, we hypothesize that interactions between Tau and the Src-family tyrosine kinase, Fyn, are pathogenic in AD. Genetically reducing either Tau or Fyn is protective in AD mouse models, and a dominant negative fragment of Tau that alters Fyn localization is also protective. Here, we describe a new AlphaScreen assay and a live-cell bioluminescence resonance energy transfer (BRET) assay using a novel BRET pair for quantifying the Tau-Fyn interaction. We used these assays to map the binding site on Tau for Fyn to the fifth and sixth PXXP motifs to show that AD-associated phosphorylation at microtubule affinity regulating kinase sites increases the affinity of the Tau-Fyn interaction and to identify Tau-Fyn interaction inhibitors by high-throughput screening. This screen has identified a variety of chemically tractable hits, suggesting that the Tau-Fyn interaction may represent a good drug target for AD. PMID:25156556

  12. 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

  13. Alpha{sub s} at Low Q{sup 2} from e+e- and tau Data

    SciTech Connect

    Menke, Sven

    2001-06-04

    It has been shown in recent analyses by ALEPH [1] and OPAL [2] that precision QCD tests are possible with hadronic {tau} decays by comparing spectral moments of the hadronic decay ratio of the {tau} with QCD calculations. In principle e{sup +}e{sup -} data can be used in a similar manner by evaluating spectral moments of R. The current e{sup +}e{sup -} data is compared with the OPAL {tau} data and a prediction is made on the achievable accuracy of QCD tests with the projected precision of PEP-N [3].

  14. Kinetic and spectroscopic investigation of Co{sup II}, Ni{sup II}, and N-oxalylglycine inhibition of the Fe{sup II}/{alpha}-ketoglutarate dioxygenase, TauD

    SciTech Connect

    Kalliri, Efthalia; Grzyska, Piotr K.; Hausinger, Robert P. . E-mail: hausinge@msu.edu

    2005-12-09

    Co{sup II}, Ni{sup II}, and N-oxalylglycine (NOG) are well-known inhibitors of Fe{sup II}/{alpha}-ketoglutarate ({alpha}KG)-dependent hydroxylases, but few studies describe their kinetics and no spectroscopic investigations have been reported. Using taurine/{alpha}KG dioxygenase (TauD) as a paradigm for this enzyme family, time-dependent inhibition assays showed that Co{sup II} and Ni{sup II} follow slow-binding inhibition kinetics. Whereas Ni{sup II}-substituted TauD was non-chromophoric, spectroscopic studies of the Co{sup II}-substituted enzyme revealed a six-coordinate site (protein alone or with {alpha}KG) that became five-coordinate upon taurine addition. The Co{sup II} spectrum was not perturbed by a series of anions or oxidants, suggesting the Co{sup II} is inaccessible and could be used to stabilize the protein. NOG competed weakly (K {sub i} {approx} 290 {mu}M) with {alpha}KG for binding to TauD, with the increased electron density of NOG yielding electronic transitions for NOG-Fe{sup II}-TauD and taurine-NOG-Fe{sup II}-TauD at 380 nm ({epsilon} {sub 38} 90-105 M{sup -1} cm{sup -1}). The spectra of the NOG-bound TauD species did not change significantly upon oxygen exposure, arguing against the formation of an oxygen-bound state mimicking an early intermediate in catalysis.

  15. 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

  16. Tau neutrino propagation and tau energy loss

    SciTech Connect

    Dutta, Sharada Iyer; Huang Yiwen; Reno, Mary Hall

    2005-07-01

    Electromagnetic energy loss of tau leptons is an important ingredient for eventual tau neutrino detection from high energy astrophysical sources. Proposals have been made to use mountains as neutrino converters, in which the emerging tau decays in an air shower. We use a stochastic evaluation of both tau neutrino conversion to taus and of tau electromagnetic energy loss. We examine the effects of the propagation for monoenergetic incident tau neutrinos as well as for several neutrino power-law spectra. Our main result is a parameterization of the tau electromagnetic energy loss parameter {beta}. We compare the results from the analytic expression for the tau flux using this {beta} with other parameterizations of {beta}.

  17. Enduring involvement of tau, beta-amyloid, alpha-synuclein, ubiquitin and TDP-43 pathology in the amyotrophic lateral sclerosis/parkinsonism-dementia complex of Guam (ALS/PDC).

    PubMed

    Miklossy, Judith; Steele, John C; Yu, Sheng; McCall, Sherman; Sandberg, Glenn; McGeer, Edith G; McGeer, Patrick L

    2008-12-01

    Guam ALS/PDC is a severe tangle forming disorder endemic to Guam with features overlapping such neurodegenerative disorders as Alzheimer disease (AD), Parkinson disease (PD), progressive supranuclear palsy (PSP), ALS, corticobasal degeneration (CBD) and pallido-ponto-nigral degeneration (PPND). Since the prevalence is declining, we examined brain tissue from 35 clinically diagnosed Chamorro patients with ALS/PDC and two Chamorro controls autopsied between 1946 and 2006, to determine if distinct variations in the pathology could be identified up to this time. Although the age at autopsy increased by 4.5-5 years per decade, we identified no qualitative differences in pathological deposits with antibodies against tau, ubiquitin, A beta, alpha-synuclein and TDP-43, indicating that these more recently identified proteins have been involved in the neuropathogenesis over the past 6 decades. Tau and TDP-43 positive neuronal, oligodendroglial and astrocytic inclusions involving multiple nerve fiber tracts occurred in both the ALS and PDC types, reinforcing the concept that these forms are part of the same disorder. The results obtained may help to define the commonality of the Guam disease with other tangle forming disorders and may help in monitoring the epidemiological changes that are taking place.

  18. 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

  19. 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…

  20. 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

  1. 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.

  2. Gifted Education and National Standards: A K-5 Program Evaluation

    ERIC Educational Resources Information Center

    Harwell-Braun, Debra A.

    2010-01-01

    The purpose of this study was to conduct a program evaluation of a K-5 Gifted Education Program. Program evaluation addressed how well the gifted education program studied met the National Association of Gifted Children standards. In addition, this study included stakeholder perceptions of the current gifted education program K-5. This program…

  3. 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

  4. Tau immunotherapy and imaging.

    PubMed

    Sigurdsson, Einar M

    2014-01-01

    Disappointing findings from recent phase III trials on amyloid-β (Aβ) immunotherapy for Alzheimer's disease (AD) have shifted the focus of such treatments to the tau protein. As tau pathology correlates better with the degree of dementia than Aβ plaque burden, it is a more attractive target once cognitive impairments are evident, while Aβ therapies may be better suited for the presymptomatic phase of the disease. Over 12 years ago, we initiated a tau immunotherapy program, seeking to alleviate the functional impairments associated with tau lesions in tauopathies. We have reported that various active and passive tau immunizations diminish tau pathology and improve function, including cognition, in different mouse models. Both extra- and intracellular pathways are likely involved. The antibodies may block the spread of tau pathology via microglial phagocytosis of the antibody-tau complex and facilitate lysosomal tau clearance in neurons after endosomal uptake. We have observed such antibody internalization following intracarotid injection in mice and in various culture models. These include brain slices and primary neurons from tangle mice as well as human neuroblastoma cell lines. Antibody targeting of different intracellular protein aggregates, including α-synuclein, Aβ and superoxide dismutase has been reported by others. Now, several laboratories have confirmed and extended our findings using various active and passive tau immunizations in different models, thereby clearly establishing the feasibility of this approach for clinical trials. We are also working on imaging approaches to monitor tau pathology, its consequences and the efficacy of treatments. Dire need exists for such diagnostic methods for tauopathies. Overall, therapies and diagnostic tools targeting tau pathology have a great potential for AD and other tauopathies.

  5. Pioglitazone prevents tau oligomerization.

    PubMed

    Hamano, Tadanori; Shirafuji, Norimichi; Makino, Chiemi; Yen, Shu-Hui; Kanaan, Nicholas M; Ueno, Asako; Suzuki, Jinya; Ikawa, Masamichi; Matsunaga, Akiko; Yamamura, Osamu; Kuriyama, Masaru; Nakamoto, Yasunari

    2016-09-23

    Tau aggregation and amyloid β protein (Aβ) deposition are the main causes of Alzheimer's disease (AD). Peroxisome proliferator-activated receptor γ (PPARγ) activation modulates Aβ production. To test whether the PPARγ agonist pioglitazone (PIO) is also effective in preventing tau aggregation in AD, we used a cellular model in which wild-type tau protein (4R0N) is overexpressed (M1C cells) (Hamano et al., 2012) as well as primary neuronal cultures. PIO reduced both phosphorylated and total tau levels, and inactivated glycogen synthase kinase 3β, a major tau kinase, associated with activation of Akt. In addition, PIO decreased cleaved caspase3 and C-terminal truncated tau species by caspase, which is expected to decrease tau aggregation. A fractionation study showed that PIO reduced high molecular-weight (120 kDa), oligomeric tau species in Tris Insoluble, sarkosyl-soluble fractions. Tau decrease was reversed by adding GW9662, a PPARγ antagonist. Together, our current results support the idea that PPARγ agonists may be useful therapeutic agents for AD.

  6. 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.

  7. The Many Faces of Tau

    PubMed Central

    Morris, Meaghan; Maeda, Sumihiro; Vossel, Keith; Mucke, Lennart

    2012-01-01

    Summary While the microtubule-binding capacity of the protein tau has been known for many years, new functions of tau in signaling and cytoskeletal organization have recently emerged. In this review, we highlight these functions and the potential roles of tau in neurodegenerative disease. We also discuss the therapeutic potential of drugs targeting various aspects of tau biology. PMID:21555069

  8. 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 -}}.

  9. Spectroscopic properties of K 5Li 2UF 10

    NASA Astrophysics Data System (ADS)

    Karbowiak, M.; Gajek, Z.; Drożdżyński, J.

    2005-04-01

    A new uranium (III) fluoro-complex of the formula K 5Li 2UF 10 has been synthesised and characterised by X-ray powder diffraction and electronic absorption spectra measurements. The compound crystallises in the orthorhombic system, space group Pnma, with a = 20.723, b = 7.809, c = 6.932 Å, V = 1121.89 Å 3, Z = 4 and is isostructural with its K 5Li 2NdF 10 and K 5Li 2LaF 10 analogous. The absorption spectrum of a polycrystalline sample of K 5Li 2UF 10 was recorded at 4.2 K in the 3500-45,000 cm -1 range and is discussed. The observed crystal-field levels were assigned and fitted to parameters of the simplified angular overlap model (AOM) and next to those of a semi-empirical Hamiltonian, which was representing the combined atomic and one-electron crystal-field interactions. The starting values of the AOM parameters were obtained from ab initio calculations. The analysis of the spectra enabled the assignment of 71 crystal-field levels of U 3+ with a relatively small r.m.s. deviation of 37 cm -1. The total splitting of 714 cm -1 was calculated for the 4I 9/2 ground multiplet.

  10. 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…

  11. 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…

  12. Bringing History Home: A K-5 Curriculum Design

    ERIC Educational Resources Information Center

    Fillpot, Elise

    2009-01-01

    Bringing history home, an elementary history curriculum and professional development project, began in 2001. As originally conceived, the project's main purpose was to move history from the margins described by Bruce VanSledright into the mainstream of the K-5 school day. Seven years later, the Bringing History Home (BHH) instructional units are…

  13. 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…

  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. Characterization of tau pathologies in gray and white matter of Guam parkinsonism-dementia complex.

    PubMed

    Winton, Matthew J; Joyce, Sonali; Zhukareva, Victoria; Practico, Domenico; Perl, Daniel P; Galasko, Douglas; Craig, Ula; Trojanowski, John Q; Lee, Virginia M-Y

    2006-05-01

    Guam parkinsonism-dementia complex (PDC) is a neurodegenerative tauopathy in ethnic Chamorro residents of the Mariana Islands that manifests clinically with parkinsonism as well as dementia and is characterized neuropathologically by prominent cortical neuron loss in association with extensive telencephalic neurofibrillary tau pathology. To further characterize cortical gray and white matter tau, alpha-synuclein and lipid peroxidation pathologies in Guam PDC, we examined the brains of 17 Chamorro PDC and control subjects using biochemical and immunohistological techniques. We observed insoluble tau pathology in both gray and white matter of PDC and Guam control cases, with frontal and temporal lobes being most severely affected. Using phosphorylation dependent anti-tau antibodies, abundant tau inclusions were detected by immunohistochemistry in both neuronal and glial cells of the neocortex, while less alpha-synuclein pathology was observed in more limited brain regions. Further, in sharp contrast to Alzheimer's disease (AD), levels of the lipid peroxidation product 8, 12-iso-iPF(2alpha)-VI isoprostane were not elevated in Guam PDC brains relative to controls. Thus, although the tau pathologies of Guam PDC share similarities with AD, the composite Guam PDC neuropathology profile of tau, alpha-synuclein and 8, 12-iso-iPF(2alpha)-VI isoprostane reported here more closely resembles that seen in other tauopathies including frontotemporal dementias (FTDs), which may imply that Guam PDC and FTD tauopathies share underlying mechanisms of neurodegeneration.

  16. 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.

  17. 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).

  18. 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.

  19. 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.

  20. Secondary atmospheric tau neutrino production

    SciTech Connect

    Bulmahn, Alexander; Hall Reno, Mary

    2010-09-01

    We evaluate the flux of tau neutrinos produced from the decay of pair produced taus from incident muons using a cascade equation analysis. To solve the cascade equations, our numerical result for the tau production Z moment is given. Our results for the flux of tau neutrinos produced from incident muons are compared to the flux of tau neutrinos produced via oscillations and the direct prompt atmospheric tau neutrino flux. Results are given for both downward and upward going neutrinos fluxes and higher zenith angles are discussed. We conclude that the direct prompt atmospheric tau neutrino flux dominates these other atmospheric sources of tau neutrinos for neutrino energies larger than a few TeV for upward fluxes, and over a wider range of energy for downward fluxes.

  1. 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.

  2. 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.

  3. B Decays with tau at Belle

    SciTech Connect

    Hara, Koji

    2010-02-10

    B decays with {tau} are sensitive to a charged Higgs predicted by extensions of the Standard Model such as the Two Higgs Doublet Models and the Minimal Supersymmetric Standard Model. We report measurements of the decays B+->{tau}{sup +}{nu}{sub {tau}}, B->D*{tau}{nu}{sub {tau}} and B->D{tau}{nu}{sub {tau}} using a large data sample of BB-bar pairs collected with the Belle detector at the KEKB asymmetric-energy e{sup +}e{sup -} collider. We observe a signal of B{sup 0}->D*{sup -}{tau}{sup +}{nu}{sub {tau}} decay with a significance of 5.2 {sigma} and find evidences of B{sup +}->{tau}{sup +}{nu}{sub {tau}} and D-bar{sup 0}{tau}{sup +}{nu}{sub {tau}} decays with significances more than 3 {sigma}.

  4. Tests for ''new physics'' from /tau/ spin correlation functions for /ital Z//sup 0//r arrow//tau//sup +//tau//sup /minus///r arrow/A/sup +/B/sup /minus//X

    SciTech Connect

    Nelson, C. A.

    1989-07-01

    The fundamental parameters /xi//sub /ital A//, /xi//sub /ital B//, and /alpha//sub /ital H// can be independently determined by measurement of the energy correlation function /ital I/(/ital E//sub /ital A//,/ital E//sub /ital B//) where /xi/ is the Michel polarization parameter for /tau//sup /minus///r arrow/scrl/sup /minus///nu//bar /nu//,/xi//sub /ital A//=(/vert bar/g/sub L//vert bar//sup 2//minus//vert bar/g/sub R//vert bar//sup 2/)(/vert bar//ital g//sub /ital L///vert bar//sup 2/+/vert bar/g/sub R//vert bar//sup 2/) is the chiral polarization parameter for /tau//sup /minus///r arrow/A/sup /minus///nu/, and /alpha//sub /ital H///congruent//minus/2a/sub /tau//v/sub /tau///(a/sub /tau///sup 2/+v/sub /tau///sup 2/) where /ital a//sub /tau//, /ital v//sub /tau// describe /ital Z//sup 0//r arrow//tau//sup +//tau//sup /minus// at the tree level. In contrast, measurement of /ital I/(/ital E//sub /ital A//) by the /tau/-polarization technique only determines /xi//sub /ital A///alpha//sub H/. For 10/sup 7/ Z/sup 0/ events and for sin/sup 2//theta//sub W/=0.23, the ideal statistical percentage errors in the determination of the Michel parameters are for /xi/, 2.6%; for /delta/, 3.5%; and for /rho/, 1.0%; and of the chiral parameters are for /xi//sub /pi//, 1.4%; for /xi//sub /rho//, 3.0%; and for /xi//sub /ital K//sup *//, 18%. For /alpha//sub /ital H//, the ideal statistical error is /sigma/(/alpha//sub /ital H//)=0.005 (3.3%). Equivalently, for sin/sup 2//theta//sub W/ it is 0.3%. Explicit formulas for the full sequential decay correlation function /ital I/(/ital E//sub /bar /mu///, /ital E//sub /ital e//, cos/psi//sub /bar /mu///ital e//) are given for arbitrary /ital Z/ mass and for /ital I/(/ital E//sub /bar /mu///, /ital E//sub /ital B//) for arbitrary Michel parameters. These results can be used for analyzing the decay of a /ital Z//prime/ boson and for /ital q/bar q// modes.

  5. 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.

  6. 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

  7. Tau Lorentz Structure with Polarization at SLD

    SciTech Connect

    Abe, K

    2004-01-29

    We present a measurement of the tau neutrino helicity (h{sub {nu}{sub {tau}}}) and the Michel parameters ({rho}, {zeta} and {delta}) by analyzing the {tau} decays {tau} {yields} {pi}(K){nu}{sub {tau}}, {tau} {yields} e{bar {nu}}{sub e}{nu}{sub {tau}} and {tau} {yields} {mu}{bar {nu}}{sub {mu}} in e{sup +}e{sup -} {yields} Z{sup 0} {yields} {tau}{sup +}{tau}{sup -}. The analysis uses the 1993-1995 SLD data sample of 4316 {tau}-pair events produced with highly polarized electrons. We obtain preliminary results of h{sub {nu}{sub {tau}}} = -0.81 {+-} 0.18 {+-} 0.03, {rho} = 0.71 {+-} 0.09 {+-} 0.04, {zeta} = 1.03 {+-} 0.36 {+-} 0.05 and {zeta}{delta} = 0.84 {+-} 0.27 {+-} 0.05.

  8. 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.

  9. Analysis of the enzymatic cleavage (beta elimination) of the capsular K5 polysaccharide of Escherichia coli by the K5-specific coliphage: reexamination.

    PubMed Central

    Hänfling, P; Shashkov, A S; Jann, B; Jann, K

    1996-01-01

    The capsular K5 polysaccharide of Escherichia coli is the receptor of the capsule-specific coliphage K5, which harbors an enzyme that degrades the capsular K5 polysaccharide to a number of oligosaccharides. Analysis of the degradation products using gel permeation chromatography, the periodate-thiobarbituric acid and bicinchoninic acid reactions, and nuclear magnetic resonance spectroscopy showed that the major reaction products are hexa-, octa-, and decasaccharides with 4,5-unsaturated glucuronic acid (delta4,5GlcA) at their nonreducing end. Thus, the bacteriophage enzyme is a K5 polysaccharide lyase and not, as we had reported previously, an endo-N-acetylglucosaminidase. PMID:8755913

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. CP violation in hadronic {tau} decays

    SciTech Connect

    Datta, Alakabha; Kiers, Ken; London, David; Szynkman, Alejandro; O'Donnell, Patrick J.

    2007-04-01

    We reexamine CP violation in the {delta}S=0 decays {tau}{yields}N{pi}{nu}{sub {tau}} (N=2,3,4). We assume that the new physics (NP) is a charged Higgs boson. We show that there is no NP contribution to {tau}{yields}{pi}{pi}{nu}{sub {tau}}, which means that no CP violation is expected in this decay. On the other hand, NP can contribute to {tau}{yields}N{pi}{nu}{sub {tau}} (N=3,4). These are dominated by the intermediate resonant decays {tau}{yields}{omega}{pi}{nu}{sub {tau}}, {tau}{yields}{rho}{pi}{nu}{sub {tau}}, and {tau}{yields}a{sub 1}{pi}{nu}{sub {tau}}. We show that the only sizeable CP-violating effects which are possible are in {tau}{yields}a{sub 1}{pi}{nu}{sub {tau}}{yields}4{pi}{nu}{sub {tau}} (polarization-dependent rate asymmetry) and {tau}{yields}{omega}{pi}{nu}{sub {tau}} (triple-product asymmetry)

  15. 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....

  16. 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....

  17. 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....

  18. 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....

  19. 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....

  20. First results from the Goddard High-Resolution Spectrograph - The chromosphere of Alpha Tauri

    NASA Technical Reports Server (NTRS)

    Carpenter, Kenneth G.; Robinson, Richard D.; Wahlgren, Glenn M.; Ake, Thomas B.; Ebbets, Dennis C.

    1991-01-01

    The K5 III star Alpha Tau was observed with the Goddard High Resolution Spectrograph on November 27, 1990 as part of the Science Assessment Program for the HST. The spectra show intersystem and permitted chromospheric emission lines of semiforbidden C II and Si II, Fe II, Fe I, Ni II, and Co II. Resolved profiles of the semiforbidden C II lines indicate a complex chromospheric turbulent velocity distribution with mean value of roughly 24 km/s, while their observed wavelengths indicate a 4 km/s downflow of the semiforbidden C II plasma. Twenty-five new emission lines have been found in the 2320-2370 A region, 17 of which have been identified with the aid of Skylab data obtained above the solar limb, including four lines from Co II (UV 8) and an Fe I (UV 12) line.

  1. Measurements of the {tau} mass and the mass difference of the {tau}{sup +} and {tau}{sup -} at BABAR

    SciTech Connect

    Aubert, B.; Karyotakis, Y.; Lees, J. P.; Poireau, V.; Prencipe, E.; Prudent, X.; Tisserand, V.; 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.

    2009-11-01

    We present the result from 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, we determine the mass to be 1776.68{+-}0.12(stat){+-}0.41(syst) MeV. We 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))x10{sup -4}, where M{sub AVG}{sup {tau}} is the average value of M{sub {tau}{sup +}} and M{sub {tau}{sup -}}.

  2. Time-weighted accumulations ap(. tau. ) and Kp(. tau. )

    SciTech Connect

    Wrenn, G.L. )

    1987-09-01

    The planetary geomagnetic indices Kp and ap are widely used in space geophysics. They provide an estimate of maximum magnetic perturbation within a 3-hour period. Many geophysical properties are clearly related to the indices, through energy transfer from a common disturbance source, but direct correlation is often lacking because of poor matching between the frequency of sampling and the physical response functions. The index ap({tau}) is a simple accumulation of the linear ap calculated with an attenuation factor {tau} included to take account of natural temporal relaxation. The case for ap({tau}) and the related Kp({tau}) is made using applications to the variability of the plasma environment in the ionosphere and inner magnetosphere. These examples of improved correlation suggest that time-weighted integration might profitably be applied to other indices.

  3. 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}}.

  4. Therapeutic strategies for tau mediated neurodegeneration

    PubMed Central

    Yoshiyama, Yasumasa; Lee, Virginia M Y; Trojanowski, John Q

    2014-01-01

    Based on the amyloid hypothesis, controlling β-amyloid protein (Aβ) accumulation is supposed to suppress downstream pathological events, tau accumulation, neurodegeneration and cognitive decline. However, in recent clinical trials, Aβ removal or reducing Aβ production has shown limited efficacy. Moreover, while active immunisation with Aβ resulted in the clearance of Aβ, it did not prevent tau pathology or neurodegeneration. This prompts the concern that it might be too late to employ Aβ targeting therapies once tau mediated neurodegeneration has occurred. Therefore, it is timely and very important to develop tau directed therapies. The pathomechanisms of tau mediated neurodegeneration are unclear but hyperphosphorylation, oligomerisation, fibrillisation and propagation of tau pathology have been proposed as the likely pathological processes that induce loss of function or gain of toxic function of tau, causing neurodegeneration. Here we review the strategies for tau directed treatments based on recent progress in research on tau and our understanding of the pathomechanisms of tau mediated neurodegeneration. PMID:23085937

  5. Closing the tau loop: the missing tau mutation

    PubMed Central

    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

    2015-01-01

    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

  6. 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

  7. Tau Induces Cooperative Taxol Binding to Microtubules

    NASA Astrophysics Data System (ADS)

    Ross, Jennifer; Santangelo, Christian; Victoria, Makrides; Fygenson, Deborah

    2004-03-01

    Taxol and tau are two ligands which stabilize the microtubule (MT) lattice. Taxol is an anti-mitotic drug that binds β tubulin in the MT interior. Tau is a MT-associated protein that binds both α and β tubulin on the MT exterior. Both taxol and tau reduce MT dynamics and promote tubulin polymerization. Tau alone also acts as a buttress to bundle, stiffen, and space MTs. A structural study recently suggested that taxol and tau may interact by binding to the same site. Using fluorescence recovery after photobleaching, we find that tau induces taxol to bind MTs cooperatively depending on the tau concentration. We develop a model that correctly fits the data in the absence of tau and yields a measure of taxol cooperativity when tau is present.

  8. 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

  9. 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.

  10. 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

  11. 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

  12. 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…

  13. 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

  14. Congeneric and (Essentially) Tau-Equivalent Estimates of Score Reliability: What They Are and How to Use Them

    ERIC Educational Resources Information Center

    Graham, James M.

    2006-01-01

    Coefficient alpha, the most commonly used estimate of internal consistency, is often considered a lower bound estimate of reliability, though the extent of its underestimation is not typically known. Many researchers are unaware that coefficient alpha is based on the essentially tau-equivalent measurement model. It is the violation of the…

  15. 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.

  16. Isoelectric point differentiates PHF-tau from biopsy-derived human brain tau proteins.

    PubMed

    Sergeant, N; Bussière, T; Vermersch, P; Lejeune, J P; Delacourte, A

    1995-11-13

    In the present study, Tau proteins were detected by two monoclonal antibodies AD2 and Tau-1 raised against PHF-tau and normal Tau proteins respectively using single- and two-dimensional immunoblotting. We demonstrate here the presence of a Tau triplet in brain homogenates from patients with Alzheimer's disease (AD) processed human brain biopsies from controls. However PHF-tau proteins have a slight but significantly higher mol. wt and a much more acidic isoelectric point. Therefore, Tau proteins are more phosphorylated in AD.

  17. Observation of the Semileptonic Decays B{yields}D*{tau}{sup -}{nu}{sub {tau}} and Evidence for B{yields}D{tau}{sup -}{nu}{sub {tau}}

    SciTech Connect

    Aubert, B.; Bona, M.; Boutigny, D.; Karyotakis, Y.; Lees, J. P.; Poireau, V.; Prudent, X.; Tisserand, V.; Zghiche, A.; Lopez, L.; Palano, A.; Pappagallo, M.; Eigen, G.; Stugu, B.; Sun, L.; Abrams, G. S.; Battaglia, M.; Brown, D. N.

    2008-01-18

    We present measurements of the semileptonic decays B{sup -}{yields}D{sup 0}{tau}{sup -}{nu}{sub {tau}}, B{sup -}{yields}D*{sup 0}{tau}{sup -}{nu}{sub {tau}}, B{sup 0}{yields}D{sup +}{tau}{sup -}{nu}{sub {tau}}, and B{sup 0}{yields}D*{sup +}{tau}{sup -}{nu}{sub {tau}}, which are potentially sensitive to non-standard model amplitudes. The data sample comprises 232x10{sup 6} {upsilon}(4S){yields}BB decays collected with the BABAR detector. From a combined fit to B{sup -} and B{sup 0} channels, we obtain the branching fractions B(B{yields}D{tau}{sup -}{nu}{sub {tau}})=(0.86{+-}0.24{+-}0.11{+-}0.06)% and B(B{yields}D*{tau}{sup -}{nu}{sub {tau}})=(1.62{+-}0.31{+-}0.10{+-}0.05)% (normalized for the B{sup 0}), where the uncertainties are statistical, systematic, and normalization-mode-related.

  18. 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.

  19. Tau binds ATP and induces its aggregation.

    PubMed

    Farid, Mina; Corbo, Christopher P; Alonso, Alejandra Del C

    2014-02-01

    Tau is a microtubule-associated protein mainly found in neurons. The protein is associated with process of microtubule assembly, which plays an important role in intracellular transport and cell structure of the neuron. Tauopathies are a group of neurodegenerative diseases specifically associated with tau abnormalities. While a well-defined mechanism remains unknown, most facts point to tau as a prominent culprit in neurodegeneration. In most cases of Tauopathies, aggregates of hyperphosphorylated tau have been found. Two proposals are present when discussing tau toxicity, one being the aggregation of tau proteins and the other points toward a conformational change within the protein. Previous work we carried out showed tau hyperphosphorylation promotes tau to behave abnormally resulting in microtubule assembly disruption as well as a breakdown in tau self-assembly. We found that tau's N-terminal region has a putative site for ATP/GTP binding. In this paper we demonstrate that tau is able to bind ATP and not GTP, that this binding induces tau self-assembly into filaments. At 1 mM ATP the filaments are 4-7 nm in width, whereas at 10 mM ATP the filaments appeared to establish lateral interaction, bundling and twisting, forming filaments that resembled the Paired Helical Filaments (PHF) isolated from Alzheimer disease brain. ATP-induced self-assembly is not energy dependent because the nonhydrolysable analogue of the ATP induces the same assembly. PMID:24258797

  20. 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.

  1. 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.

  2. 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 \

  3. 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}.

  4. 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

  5. Measurement of the semileptonic decays B{yields}D{tau}{sup -}{nu}{sub {tau}} and B{yields}D*{tau}{sup -}{nu}{sub {tau}}

    SciTech Connect

    Aubert, B.; Bona, M.; Karyotakis, Y.; Lees, J. P.; Poireau, V.; Prencipe, E.; Prudent, X.; Tisserand, V.; Lopez, L.; Palano, A.; Pappagallo, M.; Eigen, G.; Stugu, B.; Sun, L.; Abrams, G. S.; Battaglia, M.; Brown, D. N.; Jacobsen, R. G.

    2009-05-01

    We present measurements of the semileptonic decays B{sup -}{yields}D{sup 0}{tau}{sup -}{nu}{sub {tau}}, B{sup -}{yields}D*{sup 0}{tau}{sup -}{nu}{sub {tau}}, B{sup 0}{yields}D{sup +}{tau}{sup -}{nu}{sub {tau}}, and B{sup 0}{yields}D*{sup +}{tau}{sup -}{nu}{sub {tau}}, which are sensitive to non-standard model amplitudes in certain scenarios. The data sample consists of 232x10{sup 6} {upsilon}(4S){yields}BB decays collected with the BABAR detector at the PEP-II e{sup +}e{sup -} collider. We select events with a D or D* meson and a light lepton (l=e or {mu}) recoiling against a fully reconstructed B meson. We perform a fit to the joint distribution of lepton momentum and missing mass squared to distinguish signal B{yields}D{sup (*)}{tau}{sup -}{nu}{sub {tau}}({tau}{sup -}{yields}l{sup -}{nu}{sub l}{nu}{sub {tau}}) events from the backgrounds, predominantly B{yields}D{sup (*)}l{sup -}{nu}{sub l}. We measure the branching-fraction ratios R(D){identical_to}B(B{yields}D{tau}{sup -}{nu}{sub {tau}})/B(B{yields}Dl{sup -}{nu}{sub l}) and R(D{sup *}){identical_to}B(B{yields}D*{tau}{sup -}{nu}{sub {tau}})/B(B{yields}D*l{sup -}{nu}{sub l}) and, from a combined fit to B{sup -} and 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}l{sup -}{nu}{sub l} branching fractions, we obtain B(B{yields}D{tau}{sup -}{nu}{sub {tau}})=(0.86{+-}0.24{+-}0.11{+-}0.06)% and B(B{yields}D*{tau}{sup -}{nu}{sub {tau}})=(1.62{+-}0.31{+-}0.10{+-}0.05)%, where the additional third uncertainty is from the normalization mode. We also present, for the first time, distributions of the lepton momentum, |p{sub l}{sup *}|, and the squared momentum transfer, q{sup 2}.

  6. 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.

  7. 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.

  8. Advances in tau-based drug discovery

    PubMed Central

    Noble, Wendy; Pooler, Amy M.; Hanger, Diane P.

    2011-01-01

    Introduction Tauopathies, including Alzheimer’s disease (AD) and some frontotemporal dementias, are neurodegenerative diseases characterised by pathological lesions comprised of tau protein. There is currently a significant and urgent unmet need for disease-modifying therapies for these conditions and recently attention has turned to tau as a potential target for intervention. Areas covered Increasing evidence has highlighted pathways associated with tau-mediated neurodegeneration as important targets for drug development. Here, the authors review recently published papers in this area and summarise the genetic and pharmacological approaches that have shown efficacy in reducing tau-associated neurodegeneration. These include the use of agents to prevent abnormal tau processing and increase tau clearance, therapies targeting the immune system, and the manipulation of tau pre-mRNA to modify tau isoform expression. Expert opinion Several small molecule tau-based treatments are currently being assessed in clinical trials, the outcomes of which are eagerly awaited. Current evidence suggests that therapies targeting tau are likely, at least in part, to form the basis of an effective and safe treatment for Alzheimer’s disease and related neurodegenerative disorders in which tau deposition is evident. PMID:22003359

  9. Bimolecular Fluorescence Complementation; Lighting-Up Tau-Tau Interaction in Living Cells

    PubMed Central

    Tak, HyeJin; Haque, Md. Mamunul; Kim, Min Jung; Lee, Joo Hyun; Baik, Ja-Hyun; Kim, YoungSoo; Kim, Dong Jin; Grailhe, Regis; Kim, Yun Kyung

    2013-01-01

    Abnormal tau aggregation is a pathological hallmark of many neurodegenerative disorders and it is becoming apparent that soluble tau aggregates play a key role in neurodegeneration and memory impairment. Despite this pathological importance, there is currently no single method that allows monitoring soluble tau species in living cells. In this regard, we developed a cell-based sensor that visualizes tau self-assembly. By introducing bimolecular fluorescence complementation (BiFC) technique to tau, we were able to achieve spatial and temporal resolution of tau-tau interactions in a range of states, from soluble dimers to large aggregates. Under basal conditions, tau-BiFC cells exhibited little fluorescence intensity, implying that the majority of tau molecules exist as monomers. Upon chemically induced tau hyperphosphorylation, BiFC fluorescence greatly increased, indicating an increased level of tau-tau interactions. As an indicator of tau assembly, our BiFC sensor would be a useful tool for investigating tau pathology. PMID:24312574

  10. 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

  11. B vitamin deficiency promotes tau phosphorylation through regulation of GSK3beta and PP2A.

    PubMed

    Nicolia, Vincenzina; Fuso, Andrea; Cavallaro, Rosaria A; Di Luzio, Andrea; Scarpa, Sigfrido

    2010-01-01

    Neurofibrillary tangles (NFTs), composed of intracellular filamentous aggregates of hyperphosphorylated protein tau, are one of the pathological hallmarks of Alzheimer's disease (AD). Tau phosphorylation is regulated by the equilibrium between activities of its protein kinases and phosphatases; unbalance of these activities is proposed to be a reasonable causative factor to the disease process. Glycogen synthase kinase 3beta (GSK3beta) is one of the most important protein kinase in regulating tau phosphorylation; overexpression of active GSK3beta causes ADlike hyperphosphorylation of tau. Protein phosphatase 2A (PP2A) is the major phosphatase that dephosphorylates tau; it was demonstrated that highly conserved carboxyl-terminal sequence of PP2A C-subunit is a focal point for phosphatase regulation. This is the site of a reversible methyl esterification reaction that controls AB_{alpha}C heterotrimers formation. Here we demonstrate that GSK3beta and PP2A genes were upregulated by inhibiting methylation reactions through B vitamin deficiency. In this condition, methylated catalytic subunit PP2Ac was decreased, leading to reduced PP2A activity. By contrast, we observed GSK3beta protein increase and a modulation in phosphorylation sites that regulate GSK3beta activity. Therefore, one-carbon metabolism alteration seems to be a cause of deregulation of the equilibrium between GSK3beta and PP2A, leading to abnormal hyperphosphorylated tau.

  12. Tau interaction with microtubules in vivo.

    PubMed

    Samsonov, Andrey; Yu, Jiang-Zhou; Rasenick, Mark; Popov, Sergey V

    2004-12-01

    Tau is a major microtubule-associated protein which induces bundling and stabilization of axonal microtubules (MTs). To investigate the interaction of tau with MTs in living cells, we expressed GFP-tau fusion protein in cultured Xenopus embryo neurons and performed time-lapse imaging of tau-labeled MTs. Tau uniformly labeled individual MTs regardless of their assembly/disassembly status and location along the axon. Photobleaching experiments indicated that interaction of tau with MTs is very dynamic, with a half-time of fluorescence recovery of the order of 3 seconds. Treatment of cells with taxol, a drug that suppresses MT dynamics, rapidly induced detachment of tau from MTs. Although binding of tau to straight MTs was uniform, there was a heightened concentration of tau at the sites of high MT curvature. Our results suggest that dynamic interaction of tau with MTs may modify local mechanical properties of individual MTs and play a crucial role in the remodeling of the MT cytoskeleton during neuronal plasticity.

  13. Pathways by which Abeta facilitates tau pathology.

    PubMed

    Blurton-Jones, Mathew; Laferla, Frank M

    2006-12-01

    Since the initial description one hundred years ago by Dr. Alois Alzheimer, the disorder that bears his name has been characterized by the occurrence of two brain lesions: amyloid plaques and neurofibrillary tangles (NFTs). Yet the precise relationship between beta-amyloid (Abeta) and tau, the two proteins that accumulate within these lesions, has proven elusive. Today, a growing body of work supports the notion that Abeta may directly or indirectly interact with tau to accelerate NFT formation. Here we review recent evidence that Abeta can adversely affect distinct molecular and cellular pathways, thereby facilitating tau phosphorylation, aggregation, mis-localization, and accumulation. Studies are presented that support four putative mechanisms by which Abeta may facilitate the development of tau pathology. A great deal of work suggests that Abeta may drive tau pathology by activating specific kinases, providing a straightforward mechanism by which Abeta may enhance tau hyperphosphorylation and NFT formation. In the AD brain, Abeta also triggers a massive inflammatory response and pro-inflammatory cytokines can in turn indirectly modulate tau phosphorylation. Mounting evidence also suggests that Abeta may inhibit tau degradation via the proteasome. Lastly, Abeta and tau may indirectly interact at the level of axonal transport and evidence is presented for two possible scenarios by which axonal transport deficits may play a role. We propose that the four putative mechanisms described in this review likely mediate the interactions between Abeta and tau, thereby leading to the development of AD neurodegeneration.

  14. 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.

  15. 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

  16. Interaction of Escherichia coli K1 and K5 with Acanthamoeba castellanii Trophozoites and Cysts

    PubMed Central

    Matin, Abdul

    2011-01-01

    The existence of symbiotic relationships between Acanthamoeba and a variety of bacteria is well-documented. However, the ability of Acanthamoeba interacting with host bacterial pathogens has gained particular attention. Here, to understand the interactions of Escherichia coli K1 and E. coli K5 strains with Acanthamoeba castellanii trophozoites and cysts, association assay, invasion assay, survival assay, and the measurement of bacterial numbers from cysts were performed, and nonpathogenic E. coli K12 was also applied. The association ratio of E. coli K1 with A. castellanii was 4.3 cfu per amoeba for 1 hr but E. coli K5 with A. castellanii was 1 cfu per amoeba for 1 hr. By invasion and survival assays, E. coli K5 was recovered less than E. coli K1 but still alive inside A. castellanii. E. coli K1 and K5 survived and multiplied intracellularly in A. castellanii. The survival assay was performed under a favourable condition for 22 hr and 43 hr with the encystment of A. castellanii. Under the favourable condition for the transformation of trophozoites into cysts, E. coli K5 multiplied significantly. Moreover, the pathogenic potential of E. coli K1 from A. castellanii cysts exhibited no changes as compared with E. coli K1 from A. castellanii trophozoites. E. coli K5 was multiplied in A. castellanii trophozoites and survived in A. castellanii cysts. Therefore, this study suggests that E. coli K5 can use A. castellanii as a reservoir host or a vector for the bacterial transmission. PMID:22355201

  17. Measurement of the {tau} Lepton Mass and an Upper Limit on the Mass Difference between {tau}{sup +} and {tau}{sup -}

    SciTech Connect

    Belous, K.; Shapkin, M.; Sokolov, A.; Abe, K.; Adachi, I.; Gershon, T.; Haba, J.; Hazumi, M.; Itoh, R.; Iwasaki, Y.; Katayama, N.; Kichimi, H.; Krokovny, P.; Nakao, M.; Nakazawa, H.; Nishida, S.; Ozaki, H.; Sakai, Y.; Suzuki, S. Y.; Takasaki, F.

    2007-07-06

    The mass of the {tau} lepton has been measured in the decay mode {tau}{yields}3{pi}{nu}{sub {tau}} using a pseudomass technique. The result obtained from 414 fb{sup -1} of data collected with the Belle detector is M{sub {tau}}=[1776.61{+-}0.13(stat){+-}0.35(sys)] MeV/c{sup 2}. The upper limit on the relative mass difference between positive and negative {tau} leptons is vertical bar M{sub {tau}{sup +}}-M{sub {tau}{sup -}} vertical bar/M{sub {tau}}<2.8x10{sup -4} at 90% confidence level.

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. B to tau Leptonic and Semileptonic Decays

    SciTech Connect

    Barrett, M.; /Brunel U.

    2011-11-17

    Decays of B mesons to states involving {tau} leptons can be used as a tool to search for the effects of new physics, such as those involving a charged Higgs boson. The experimental status of the decays B {yields} {tau}{nu} and B {yields} D{sup (*)}{tau}{nu} is discussed, together with limits on new physics effects from current results. Leptonic and semileptonic decays of B mesons into states involving {tau} leptons remain experimentally challenging, but can prove a useful tool for constraining Standard Model parameters, and also offer to constrain the effects of any new physics that may exist including the presence of a charged Higgs boson.

  3. 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.

  4. Caspase-cleaved tau exhibits rapid memory impairment associated with tau oligomers in a transgenic mouse model.

    PubMed

    Kim, YoungDoo; Choi, Hyunwoo; Lee, WonJae; Park, Hyejin; Kam, Tae-In; Hong, Se-Hoon; Nah, Jihoon; Jung, Sunmin; Shin, Bora; Lee, Huikyong; Choi, Tae-Yong; Choo, Hyosun; Kim, Kyung-Keun; Choi, Se-Young; Kayed, Rakez; Jung, Yong-Keun

    2016-03-01

    In neurodegenerative diseases like AD, tau forms neurofibrillary tangles, composed of tau protein. In the AD brain, activated caspases cleave tau at the 421th Asp, generating a caspase-cleaved form of tau, TauC3. Although TauC3 is known to assemble rapidly into filaments in vitro, a role of TauC3 in vivo remains unclear. Here, we generated a transgenic mouse expressing human TauC3 using a neuron-specific promoter. In this mouse, we found that human TauC3 was expressed in the hippocampus and cortex. Interestingly, TauC3 mice showed drastic learning and spatial memory deficits and reduced synaptic density at a young age (2-3months). Notably, tau oligomers as well as tau aggregates were found in TauC3 mice showing memory deficits. Further, i.p. or i.c.v. injection with methylene blue or Congo red, inhibitors of tau aggregation in vitro, and i.p. injection with rapamycin significantly reduced the amounts of tau oligomers in the hippocampus, rescued spine density, and attenuated memory impairment in TauC3 mice. Together, these results suggest that TauC3 facilitates early memory impairment in transgenic mice accompanied with tau oligomer formation, providing insight into the role of TauC3 in the AD pathogenesis associated with tau oligomers and a useful AD model to test drug candidates.

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

    PubMed

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

    2015-06-01

    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.

  6. 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

  7. 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.

  8. 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

  9. Decays of the tau lepton

    SciTech Connect

    Burchat, P.R.

    1986-02-01

    Previous measurements of the branching fractions of the tau lepton result in a discrepancy between the inclusive branching fraction and the sum of the exclusive branching fractions to final states containing one charged particle. The sum of the exclusive branching fractions is significantly smaller than the inclusive branching fraction. In this analysis, the branching fractions for all the major decay modes are measured simultaneously with the sum of the branching fractions constrained to be one. The branching fractions are measured using an unbiased sample of tau decays, with little background, selected from 207 pb/sup -1/ of data accumulated with the Mark II detector at the PEP e/sup +/e/sup -/ storage ring. The sample is selected using the decay products of one member of the ..gamma../sup +/..gamma../sup -/ pair produced in e/sup +/e/sup -/ annihilation to identify the event and then including the opposite member of the pair in the sample. The sample is divided into subgroups according to charged and neutral particle multiplicity, and charged particle identification. The branching fractions are simultaneously measured using an unfold technique and a maximum likelihood fit. The results of this analysis indicate that the discrepancy found in previous experiments is possibly due to two sources. First, the leptonic branching fractions measured in this analysis are about one standard deviation higher than the world average. The measured leptonic branching fractions correspond to a tau lifetime of (3.0 +- 0.2) x 10/sup -13/ s. Secondly, the total branching fraction to one charged hadron plus at least one neutral particle is measured to be (7 +- 3)% higher than the branching fraction expected from a combination of previous measurements and theoretical predictions. It is shown that decay modes involving the eta are not expected to contribute more than 3% to this excess.

  10. The Microjet of AA Tau

    NASA Astrophysics Data System (ADS)

    Cox, A. W.; Hilton, G. M.; Williger, G. M.; Grady, C. A.; Woodgate, B.

    2005-12-01

    The microjet of AA Tau A.W. Cox (Atholton High School, Columbia MD), G.M. Hilton (SSAI and GSFC), G.M. Williger (JHU and U. Louisville), C.A. Grady (Eureka Scientific and GSFC) B.Woodgate (NASA's GSFC) AA Tau is a classical T Tauri star with a spatially resolved disk viewed at approximately 70 degrees from pole-on. Photo-polarimetric variability of the star has been interpreted as being caused by the stellar magnetic field being inclined at 30 degrees with respect to the stellar rotation axis, producing a warp in the inner disk. Under these conditions, any jet should be less collimated than typical of T Tauri microjets, and should show signs of the jet axis precessing around the stellar rotation axis. When compared with the microjets imaged in the HST/STIS coronagraphic imaging survey, the AA Tau jet has an opening half-angle of approximately 10-15 degrees rather than the 3-5 degrees typical of the other T Tauri stars which have been coronagraphically imaged by HST/STIS. Using the HST data with ultra-narrowband imagery and long slit spectroscopy obtained with the Goddard Fabry-Perot and the Dual Imaging Spectrograph at the Apache Point Observatory 3.5m telescope, we derive the jet inclination, knot ejection epochs, and ejection frequency. We also compare the jet opening angle with model predictions. Apache Point Observatory observations with the Goddard Fabry-Perot were made through a grant of Director's Discretionary Time. Apache Point Observatory is operated by the Astrophysical Research Consortium. The GFP was supported under NASA RTOP 51-188-01-22 to GSFC. Grady is supported under NASA contract NNH05CD30C to Eureka Scientific.

  11. 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.

  12. 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.

  13. Csf p-tau181/tau ratio as biomarker for TDP pathology in frontotemporal dementia.

    PubMed

    Borroni, Barbara; Benussi, Alberto; Archetti, Silvana; Galimberti, Daniela; Parnetti, Lucilla; Nacmias, Benedetta; Sorbi, Sandro; Scarpini, Elio; Padovani, Alessandro

    2015-03-01

    Our objective was to evaluate the CSF phospho-Tau181/total-Tau (p/t-Tau) ratio to distinguish between the two main forms of frontotemporal lobar degeneration (FTLD): FTLD with TDP-43 (FTLD-TDP) and FTLD with Tau inclusions (FTLD-Tau). CSF p/t-Tau ratio was examined in 79 FTLD patients with predictable neuropathology, i.e. Tau (affected by progressive supranuclear palsy or carriers of mutations within the MAPT gene) or TDP-43 (carriers of mutations within granulin, C9orf72, TARDBP genes or affected by FTD with motor neuron disease). FTLD patients were randomly grouped in a training cohort (n = 39) to assess the best CSF p/t-Tau cut-off score according to ROC analysis, and a validation cohort (n = 40) to evaluate accuracy values of the identified marker. Results showed that, in the training cohort, we found a significantly reduced CSF p/t-Tau ratio in FTLD-TDP relative to FTLD-Tau. ROC analysis for p/t-Tau ratio was 0.873 and cut-off score of 0.136 allowed to differentiate FTLD-TDP and FTLD-Tau with 81.8% sensitivity and 88.2% specificity, respectively. Analysis in the validation cohort showed CSF p/t-Tau ratio < 0.136 to distinguish FTLD-TDP from FTLD-Tau with 83.3% specificity and 63.6% sensitivity, respectively. The positive predictive value of detecting TDP neuropathology was 82.4%. In conclusion, a reduced CSF p/t-Tau ratio represents a viable biomarker to correctly identify TDP pathology in FTLD.

  14. Critical residues involved in tau binding to fyn: implications for tau phosphorylation in Alzheimer's disease.

    PubMed

    Lau, Dawn H W; Hogseth, Marte; Phillips, Emma C; O'Neill, Michael J; Pooler, Amy M; Noble, Wendy; Hanger, Diane P

    2016-01-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterised by neuropathological deposits of amyloid plaques and neurofibrillary tangles comprised of β-amyloid and tau protein, respectively. In AD, tau becomes abnormally phosphorylated and aggregates to form intracellular deposits. However, the mechanisms by which tau exerts neurotoxicity in disease remain unclear. Recent studies have suggested that the presence of tau at synapses may indicate a role in neuronal signalling, which could be disrupted in pathological conditions. The non-receptor-associated tyrosine kinase fyn is located at the dendrite in neurons, where it was recently shown to interact with tau to stabilise receptor complexes at the post-synaptic density. Fyn also co-localises with tau in a proportion of neurons containing tau tangles in AD and fyn is also a tau kinase. Hence, tau-fyn interactions could play a pathogenic role in AD. Here we report the identification of critical proline residues, Pro213, Pro216, and Pro219, located within the fifth and sixth Pro-X-X-Pro motifs in the proline-rich region of tau, that are important for its binding to fyn. These residues in tau are flanked by numerous phosphorylation sites and therefore we investigated the relationship between fyn and the degree of tau phosphorylation in human post-mortem brain tissue. We found no difference in the amount of fyn present in control and AD brain. Notably, however, there was a significant correlation between fyn and phosphorylated tau at specific phospho-epitopes in control, but not in AD brain. Our results suggest that the pathological mechanisms underlying AD, that result in increased tau phosphorylation, may disrupt the physiological relationship between tau phosphorylation and fyn. PMID:27193083

  15. Cerebrospinal fluid tau proteins in status epilepticus.

    PubMed

    Monti, Giulia; Tondelli, Manuela; Giovannini, Giada; Bedin, Roberta; Nichelli, Paolo F; Trenti, Tommaso; Meletti, Stefano; Chiari, Annalisa

    2015-08-01

    Tau protein is a phosphorylated microtubule-associated protein, principally localized at neuronal level in the central nervous system (CNS). Tau levels in the cerebrospinal fluid (CSF) are considered to index both axonal and neuronal damage. To date, however, no study has specifically evaluated the CSF levels of tau proteins in patients with status epilepticus (SE). We evaluated these established biomarkers of neuronal damage in patients with SE who received a lumbar puncture during SE between 2007 and 2014. Status epilepticus cases due to acute structural brain damage, including CNS infection, were excluded. Clinical, biological, therapeutic, and follow-up data were collected. Group comparison between patients stratified according to SE response to antiepileptic drugs (AEDs), disability, and epilepsy outcomes were performed. Twenty-eight patients were considered for the analyses (mean age 56 years): 14 patients had abnormally high CSF t-tau level, six patients had abnormally high CSF p-tau level, and only three patients had abnormally low Aβ1-42 level. Cerebrospinal fluid t-tau value was higher in patients who developed a refractory SE compared to patients with seizures controlled by AED. Cerebrospinal fluid t-tau values were positively correlated with SE duration and were higher in patients treated with propofol anesthesia compared to patients that had not received this treatment. Patients with higher CSF t-tau had higher risk of developing disability (OR = 32.5, p = 0.004) and chronic epilepsy (OR = 12; p = 0.016) in comparison with patients with lower CSF t-tau level. Our results suggest that CSF t-tau level might be proposed as a biomarker of SE severity and prognosis. Prospective studies are needed to evaluate the effects of propofol on tau pathology in this setting. This article is part of a Special Issue entitled "Status Epilepticus".

  16. 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

  17. 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 \

  18. 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…

  19. 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.

  20. 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…

  1. 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,…

  2. Dry Creek Joint Elementary School District. Educational Specifications: K-5 Permanent (Revised 1998).

    ERIC Educational Resources Information Center

    Dry Creek Joint Elementary School District, Roseville, CA.

    An Educational Specification Committee was convened to determine the design specifications required for a new K-5 (and temporarily 6-8 grade) elementary school in Roseville, California's Dry Creek District. This report presents revisions to an earlier document that examined school room specifications for each grade level and administrative area.…

  3. 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…

  4. 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…

  5. Mycotic aneurysm caused by gas-forming serotype K5 Klebsiella pneumoniae.

    PubMed

    Chen, Yi-Jung; Chen, Shey-Ying; Wang, Jin-Town; Hsueh, Po-Ren

    2009-03-01

    We describe the first documented case of mycotic aneurysm caused by gas-forming serotype K5, and rmpA and iuc positive Klebsiella pneumonia with a hypermucoviscosity phenotype in a diabetic patient. The patient received ceftriaxone for one month and underwent aorto-bi-iliac grafting and inferior mesenteric artery reimplantation and recovered well.

  6. A novel tau transcript in cultured human neuroblastoma cells expressing nuclear tau

    PubMed Central

    1993-01-01

    We previously reported the presence of the microtubule-associated protein, tau in the nuclei of primate cells in culture. The present study confirms the existence of nuclear tau in two human neuroblastoma cells lines by indirect immunofluorescence and Western blot using mAbs to tau. Northern blot analysis of poly A+ mRNA detects a novel 2-kb tau transcript coexpressed with the 6-kb message in cultured human cells and human frontal cortex. PCR and cDNA sequencing demonstrate that the 2-kb message contains the entire tau coding region. Furthermore, actinomycin D transcription inhibition experiments indicate that the 2- kb message is not derived from the 6-kb message, but instead arises from the original tau transcript. One of the human neuroblastoma cell lines examined contains both nuclear and cytoplasmic tau as assayed by both Western blot and indirect immunofluorescence. Northern blot analysis of this cell line indicates that copious amounts of the 2-kb message are present while little of the 6-kb transcript is obvious. Immunofluorescence analysis of this cell line demonstrates that the cytoplasmic tau is not localized to microtubules. Together, these results indicate that the 2-kb tau message in humans may specify tau for non-microtubule functions in both the cytoplasm and the nucleus. We hypothesize that this is accomplished via a message targeting mechanism mediated by the untranslated regions of the tau messages. PMID:8468346

  7. 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

  8. Tau phosphorylation affects its axonal transport and degradation

    PubMed Central

    Rodríguez-Martín, Teresa; Cuchillo-Ibáñez, Inmaculada; Noble, Wendy; Nyenya, Fanon; Anderton, Brian H.; Hanger, Diane P.

    2013-01-01

    Phosphorylated forms of microtubule-associated protein tau accumulate in neurofibrillary tangles in Alzheimer's disease. To investigate the effects of specific phosphorylated tau residues on its function, wild type or phosphomutant tau was expressed in cells. Elevated tau phosphorylation decreased its microtubule binding and bundling, and increased the number of motile tau particles, without affecting axonal transport kinetics. In contrast, reducing tau phosphorylation enhanced the amount of tau bound to microtubules and inhibited axonal transport of tau. To determine whether differential tau clearance is responsible for the increase in phosphomimic tau, we inhibited autophagy in neurons which resulted in a 3-fold accumulation of phosphomimic tau compared with wild type tau, and endogenous tau was unaffected. In autophagy-deficient mouse embryonic fibroblasts, but not in neurons, proteasomal degradation of phosphomutant tau was also reduced compared with wild type tau. Therefore, autophagic and proteasomal pathways are involved in tau degradation, with autophagy appearing to be the primary route for clearing phosphorylated tau in neurons. Defective autophagy might contribute to the accumulaton of tau in neurodegenerative diseases. PMID:23601672

  9. 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.

  10. Status of the tau one prong problem

    SciTech Connect

    Hayes, K.G.

    1989-08-01

    The present status of the tau one prong problem is reviewed. Emphasis is placed on recent published branching fraction measurements, the status and implications of tau lifetime measurements, and measurements which constrain the sum of branching fractions to be unity. 29 refs., 10 figs., 2 tabs.

  11. 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

  12. 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.

  13. Crystal Ball results on tau decays

    SciTech Connect

    Lowe, S.T.

    1987-10-01

    This report reviews measurements and upper limit determinations for a number of exclusive 1-prong tau decay modes using the Crystal Ball detector. These results are important input to the apparent discrepancy between the topological and sum-of-exclusive branching fractions in 1-prong tau decays.

  14. 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.

  15. Microglial internalization and degradation of pathological tau is enhanced by an anti-tau monoclonal antibody

    PubMed Central

    Luo, Wenjie; Liu, Wencheng; Hu, Xiaoyan; Hanna, Mary; Caravaca, April; Paul, Steven M.

    2015-01-01

    Microglia have been shown to contribute to the clearance of brain amyloid β peptides (Aβ), the major component of amyloid plaques, in Alzheimer’s disease (AD). However, it is not known whether microglia play a similar role in the clearance of tau, the major component of neurofibrillary tangles (NFTs). We now report that murine microglia rapidly internalize and degrade hyperphosphorylated pathological tau isolated from AD brain tissue in a time-dependent manner in vitro. We further demonstrate that microglia readily degrade human tau species released from AD brain sections and eliminate NFTs from brain sections of P301S tauopathy mice. The anti-tau monoclonal antibody MC1 enhances microglia-mediated tau degradation in an Fc-dependent manner. Our data identify a potential role for microglia in the degradation and clearance of pathological tau species in brain and provide a mechanism explaining the potential therapeutic actions of passively administered anti-tau monoclonal antibodies. PMID:26057852

  16. 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

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

    PubMed

    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.

  18. Coefficient alpha and interculture test selection.

    PubMed

    Thurber, Steven; Kishi, Yasuhiro

    2014-04-01

    The internal consistency reliability of a measure can be a focal point in an evaluation of the potential adequacy of an instrument for adaptation to another cultural setting. Cronbach's alpha (α) coefficient is often used as the statistical index for such a determination. However, alpha presumes a tau-equivalent test and may constitute an inaccurate population estimate for multidimensional tests. These notions are expanded and examined with a Japanese version of a questionnaire on nursing attitudes toward suicidal patients, originally constructed in Sweden using the English language. The English measure was reported to have acceptable internal consistency (α) albeit the dimensionality of the questionnaire was not addressed. The Japanese scale was found to lack tau-equivalence. An alternative to alpha, "composite reliability," was computed and found to be below acceptable standards in magnitude and precision. Implications for research application of the Japanese instrument are discussed. PMID:22523134

  19. 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

  20. 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

  1. Characteristics of Tau and Its Ligands in PET Imaging.

    PubMed

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

    2016-01-06

    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.

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. Imaging pathological tau in atypical parkinsonian disorders

    PubMed Central

    Coakeley, Sarah; Strafella, Antonio P.

    2016-01-01

    Purpose of review This review examines the current literature on tau imaging in atypical parkinsonian disorders and other tauopathies. Recent findings There are a number of tau PET radiotracers that have demonstrated promising preliminary results in atypical parkinsonian disorders, such as progressive supranuclear palsy and corticobasal degeneration. These radiotracers were capable of selectively labeling tau in vitro and in vivo, with high affinity. Other radiotracers tested more extensively in patients with Alzheimer’s disease have also been able to successfully image tau deposition. Summary The development of tau radioligands for PET has led to the current testing of these tracers in clinical studies, many of which concentrate on patients with Alzheimer’s disease. Atypical parkinsonian disorders such as progressive supranuclear palsy and corticobasal degeneration are now being investigated as well. These disorders can be very difficult to diagnose, because of their clinical overlap with other parkinsonian disorders. Imaging tau using PET could serve as a diagnostic biomarker for these tauopathies and provide a means of assessing treatment that targets tau burden. PMID:26110795

  7. Tau pathology induces intraneuronal cholesterol accumulation.

    PubMed

    Glöckner, Frauke; Ohm, Thomas G

    2014-09-01

    Epidemiologic and experimental data suggest the involvement of cholesterol metabolism in the development and progression of Alzheimer disease and Niemann-Pick type C disease, but not of frontotemporal dementias. In these 3 neurodegenerative diseases, however, protein tau hyperphosphorylation and aggregation into neurofibrillary tangles are observed. To elucidate the relationship between cholesterol and tau, we compared sterol levels of neurons burdened with neurofibrillary tangles with those of their unaffected neighbors using semiquantitative filipin fluorescence microscopy in mice expressing P301L mutant human tau (a well-described model of FTDP-17) and in P301L transgenic mice lacking apolipoprotein E (the major cholesterol transporter in the brain). Cellular unesterified cholesterol was higher in neurons affected by tau pathology irrespective of apolipoprotein E deficiency. This argues for an impact of tau pathology on cellular cholesterol homeostasis. We suggest that there is a bidirectional mode of action: Disturbances in cellular cholesterol metabolism may promote tau pathology, but tau pathology may also alter neuronal cholesterol homeostasis; once it is established, a vicious cycle may promote neurofibrillary tangle formation.

  8. Global hairpin folding of tau in solution.

    PubMed

    Jeganathan, Sadasivam; von Bergen, Martin; Brutlach, Henrik; Steinhoff, Heinz-Jürgen; Mandelkow, Eckhard

    2006-02-21

    The microtubule-associated protein tau stabilizes microtubules in its physiological role, whereas it forms insoluble aggregates (paired helical filaments) in Alzheimer's disease. Soluble tau is considered a natively unfolded protein whose residual folding and intramolecular interactions are largely undetermined. In this study, we have applied fluorescence resonance energy transfer (FRET) and electron paramagnetic resonance (EPR) to examine the proximity and flexibility of tau domains and the global folding. FRET pairs spanning the tau molecule were created by inserting tryptophans (donor) and cysteines (labeled with IAEDANS as an acceptor) by site-directed mutagenesis. The observed FRET distances were significantly different from those expected for a random coil. Notably, the C-terminal end of tau folds over into the vicinity of the microtubule-binding repeat domain, the N-terminus remains outside the FRET distance of the repeat domain, yet both ends of the molecule approach one another. The interactions between the domains were obliterated by denaturation in GdnHCl. Paramagnetic spin-labels attached in various domains of tau were analyzed by EPR and exhibited a high mobility throughout. The data indicate that tau retains some global folding even in its "natively unfolded" state, combined with the high flexibility of the chain.

  9. Probing M subdwarf metallicity with an esdK5+esdM5.5 binary

    NASA Astrophysics Data System (ADS)

    Pavlenko, Ya. V.; Zhang, Z. H.; Gálvez-Ortiz, M. C.; Kushniruk, I. O.; Jones, H. R. A.

    2015-10-01

    Context. We present a spectral analysis of the binary G 224-58 AB, which consists of the coolest M extreme subdwarf (esdM5.5) and a brighter primary (esdK5). This binary may serve as a benchmark for metallicity measurement calibrations and as a test bed for atmospheric and evolutionary models for esdM objects. Aims: We perform the analysis of optical and infrared spectra of both components to determine their parameters. Methods: We determine abundances primarily using high-resolution optical spectra of the primary. Other parameters were determined from the fits of synthetic spectra computed with these abundances to the observed spectra from 0.4 to 2.5 microns for both components. Results: We determine Teff = 4625 ± 100 K, log g = 4.5 ± 0.5 for the A component and Teff = 3200 ± 100 K, log g = 5.0 ± 0.5, for the B component. We obtained abundances of [ Mg / H ] = + - 1.51 ± 0.08, [Ca/H] = - 1.39 ± 0.03, [Ti/H] = - 1.37 ± 0.03 for alpha group elements and [CrH] = - 1.88 ± 0.07, [Mn/H] = - 1.96 ± 0.06, [ Fe / H ] = - 1.92 ± 0.02, [Ni/H] = - 1.81 ± 0.05 and [Ba/H] = - 1.87 ± 0.11 for iron group elements from fits to the spectral lines observed in the optical and infrared spectral regions of the primary. We find consistent abundances with fits to the secondary albeit at lower signal to noise. Conclusions: Abundances of different elements in G 224-58 A and G 224-58 B atmospheres cannot be described by one metallicity parameter. The offset of ˜0.4 dex between the abundances derived from alpha element and iron group elements corresponds with our expectation for metal-deficient stars. We thus clarify that some indices used to date to measure metallicities for establishing esdM stars, based on CaH, MgH, and TiO band system strength ratios in the optical and H2O in the infrared, relate to abundances of alpha-element group rather than to iron peak elements. For metal deficient M dwarfs with [ Fe / H ] < - 1.0, this provides a ready explanation for apparently

  10. Intracerebral injection of preformed synthetic tau fibrils initiates widespread tauopathy and neuronal loss in the brains of tau transgenic mice

    PubMed Central

    Peeraer, Eve; Bottelbergs, Astrid; Van Kolen, Kristof; Stancu, Ilie-Cosmin; Vasconcelos, Bruno; Mahieu, Michel; Duytschaever, Hilde; Ver Donck, Luc; Torremans, An; Sluydts, Ellen; Van Acker, Nathalie; Kemp, John A.; Mercken, Marc; Brunden, Kurt R.; Trojanowski, John Q.; Dewachter, Ilse; Lee, Virginia M.Y.; Moechars, Diederik

    2015-01-01

    Neurofibrillary tangles composed of hyperphosphorylated fibrillized tau are found in numerous tauopathies including Alzheimer's disease. Increasing evidence suggests that tau pathology can be transmitted from cell-to-cell; however the mechanisms involved in the initiation of tau fibrillization and spreading of disease linked to progression of tau pathology are poorly understood. We show here that intracerebral injections of preformed synthetic tau fibrils into the hippocampus or frontal cortex of young tau transgenic mice expressing mutant human P301L tau induces tau hyperphosphorylation and aggregation around the site of injection, as well as a time-dependent propagation of tau pathology to interconnected brain areas distant from the injection site. Furthermore, we show that the tau pathology as a consequence of injection of tau preformed fibrils into the hippocampus induces selective loss of CA1 neurons. Together, our data confirm previous studies on the seeded induction and the spreading of tau pathology in a different tau transgenic mouse model and reveals neuronal loss associated with seeded tau pathology in tau transgenic mouse brain. These results further validate the utility of the tau seeding model in studying disease transmission, and provide a more complete in vivo tauopathy model with associated neurodegeneration which can be used to investigate the mechanisms involved in tau aggregation and spreading, as well as aid in the search for disease modifying treatments for Alzheimer's disease and related tauopathies. PMID:25220759

  11. 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…

  12. 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

  13. Tau Lepton Flavor Violation Results from BaBar

    SciTech Connect

    Cervelli, A.; /INFN, Pisa

    2012-04-03

    We report the recent results obtained by BABAR collaboration in lepton flavor violation (LFV) searches in the tau lepton sector, presenting 16 new results from {tau}{sub LLL} (L = e, {mu}), {tau} {yields} LV{sup 0} V{sup 0} = {rho}{sup 0}, K*{sup 0}, K*{sup -0}, {Phi} and {tau} {yields} lK{sub S}.

  14. Hyperphosphorylation and Cleavage at D421 Enhance Tau Secretion

    PubMed Central

    Rivest-McGraw, Jessica; Bertrand, Johanne; Lauzon, Michel; Leclerc, Nicole

    2012-01-01

    It is well established that tau pathology propagates in a predictable manner in Alzheimer’s disease (AD). Moreover, tau accumulates in the cerebrospinal fluid (CSF) of AD’s patients. The mechanisms underlying the propagation of tau pathology and its accumulation in the CSF remain to be elucidated. Recent studies have reported that human tau was secreted by neurons and non-neuronal cells when it was overexpressed indicating that tau secretion could contribute to the spreading of tau pathology in the brain and could lead to its accumulation in the CSF. In the present study, we showed that the overexpression of human tau resulted in its secretion by Hela cells. The main form of tau secreted by these cells was cleaved at the C-terminal. Surprisingly, secreted tau was dephosphorylated at several sites in comparison to intracellular tau which presented a strong immunoreactivity to all phospho-dependent antibodies tested. Our data also revealed that phosphorylation and cleavage of tau favored its secretion by Hela cells. Indeed, the mimicking of phosphorylation at 12 sites known to be phosphorylated in AD enhanced tau secretion. A mutant form of tau truncated at D421, the preferential cleavage site of caspase-3, was also significantly more secreted than wild-type tau. Taken together, our results indicate that hyperphosphorylation and cleavage of tau by favoring its secretion could contribute to the propagation of tau pathology in the brain and its accumulation in the CSF. PMID:22615831

  15. 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.

  16. Quantitative characterization of heparin binding to Tau protein: implication for inducer-mediated Tau filament formation.

    PubMed

    Zhu, Hai-Li; Fernández, Cristina; Fan, Jun-Bao; Shewmaker, Frank; Chen, Jie; Minton, Allen P; Liang, Yi

    2010-02-01

    Neurofibrillary tangles, principally composed of bundles of filaments formed by the microtubule-associated protein Tau, are a hallmark of a group of neurodegenerative diseases such as Alzheimer disease. Polyanionic cofactors such as heparin can induce Tau filament formation in vitro. Here we quantitatively characterize the interaction between recombinant human Tau fragment Tau(244-372) and heparin (average molecular mass = 7 kDa) as well as heparin-induced fibril formation by using static light scattering, isothermal titration calorimetry, turbidity assays, and transmission electron microscopy. Our data clearly show that at physiological pH, heparin 7K, and human Tau(244-372) form a tight 1:1 complex with an equilibrium association constant exceeding 10(6) m(-1) under reducing conditions, triggering Tau fibrillization. In the absence of dithiothreitol, heparin shows a moderate binding affinity (10(5) m(-1)) to Tau(244-372), similarly triggering Tau fibrillization. Further fibrillization kinetics analyses show that the lag time appears to be approximately invariant up to a molar ratio of 2:1 and then increases at larger ratios of heparin/Tau. The maximum slope representing the apparent rate constant for fibril growth increases sharply with substoichiometric ratios of heparin/Tau and then decreases to some extent with ratios of >1:1. The retarding effect of heparin in excess is attributed to the large increase in ionic strength of the medium arising from free heparin. Together, these results suggest that the formation of the 1:1 complex of Tau monomer and heparin plays an important role in the inducer-mediated Tau filament formation, providing clues to understanding the pathogenesis of neurodegenerative diseases.

  17. 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

  18. 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.

  19. 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.

  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.

  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. Constitutive secretion of tau protein by an unconventional mechanism.

    PubMed

    Chai, Xiyun; Dage, Jeffrey L; Citron, Martin

    2012-12-01

    The microtubule-associated protein tau plays a critical role in the pathogenesis of Alzheimer's disease and several related disorders. In the disease tau aggregates into paired helical and straight filaments, which can form higher order neurofibrillary tangles in neurons and this pathology is associated with progressive neuronal loss and cognitive decline. Tau is a cytoplasmic protein and is thought to be released only from degenerating cells. In contrast, here we provide evidence that tau is constitutively secreted at a low level. We directly show tau release in cell culture model systems. In inducible transfected cell lines we observe that a small proportion of full-length tau is released from intact cells in a time dependent manner. We show that this tau is released by an unconventional secretion process, as the release is temperature dependent but not blocked by inhibitors of the conventional secretory pathway. We characterize the released tau as full length, not vesicle associated and containing Phospho-Tau (181P) proportional to its intracellular concentration. We demonstrate that tau secretion and its suppression by low temperature also occurs in human neurons differentiated from induced pluripotent stem cells. The constitutive tau secretion that we propose provides the most parsimonious explanation for the observed presence of tau in the CSF of healthy animals and human beings. If previously postulated pathogenic extracellular tau intermediates are released by this route, low level constitutive tau secretion could play a role in the spread of tau pathology in Alzheimer's disease and other human tauopathies. PMID:22668776

  4. 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.

  5. Nucleotide fluctuation of RecA repair gene in Siberian permafrost Psychrobacter cryohalolentis K5

    NASA Astrophysics Data System (ADS)

    Tremberger, George, Jr.; Holden, T.; Cheung, E.; Subramaniam, R.; Sullivan, R.; Schneider, P.; Flamholz, A.; Marchese, P.; Lieberman, D.; Cheung, T.

    2008-08-01

    A nucleotide sequence can be expressed as a numerical sequence when each nucleotide is assigned its proton number. A resulting gene numerical sequence can be investigated for its fractal dimension in terms of evolution and chemical properties for comparative studies. We have investigated such nucleotide fluctuation in the RecA repair gene of Psychrobacter cryohalolentis K5, Psychrobacter arcticus 273-4, and Psychrobacter sp. PRwf-1. The fractal dimension was found to correlate with the gene's operating temperature with the highest fractal dimension associated with P. cryohalolentis K5 living at the low temperatures found in Siberian permafrost. The CpG dinucleotide content was found to be about 5% for the three species of Psychrobacters, which is substantially lower than that of Deinococcus radiodurans at about 12%. The average nucleotide pair-wise free energy was found to be lowest for Psychrobacter sp. PRwf-1, the species with the lowest fractal dimension of the three, consistent with the recent finding that Psychrobacter sp. PRw-f1 has a temperature growth maximum of 15-20°C higher than P. arcticus 273-4 and P. cryohaloentis K5. The results suggest that microbial vitality in extreme environments is associated with fractal dimension as well as high CpG dinucleotide content, while the average nucleotide pair-wise free energy is related to the operating environment. Evidence that extreme temperature operation would impose constraints measurable by Shannon entropy is also discussed. A quantitative estimate of an entropy-based measure having the characteristics of a mechanical pressure shows that the Psychrobacter RecA sequence experiences lower pressure than that of the human HAR1 sequence.

  6. 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

  7. 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.

  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. Is the Sky Really Falling?: An Update on the Status of Social Studies in the K-5 Curriculum in Indiana

    ERIC Educational Resources Information Center

    VanFossen, Phillip J.; McGrew, Chris

    2008-01-01

    This study replicates a 2005 study of the status of social studies in the K-5 curriculum in Indiana. The current study reports the results of a comprehensive survey (33 fixed and 2 open-ended) of a stratified (by grade) random sample of K-5 teachers in Indiana (n = 385; response rate = 32%). Results indicated a continued marginalization of social…

  10. 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.

  11. Ultrahigh energy tau neutrino flux regeneration while skimming the Earth

    SciTech Connect

    Bigas, Oscar Blanch

    2008-09-15

    The detection of Earth-skimming tau neutrinos has turned into a very promising strategy for the observation of ultra-high-energy cosmic neutrinos. The sensitivity of this channel crucially depends on the parameters of the propagation of the tau neutrinos through the terrestrial crust, which governs the flux of emerging tau leptons that can be detected. One of the characteristics of this propagation is the possibility of regeneration through multiple {nu}{sub {tau}}{r_reversible}{tau} conversions, which are often neglected in the standard picture. In this paper, we solve the transport equations governing the {nu}{sub {tau}} propagation and compare the flux of emerging tau leptons obtained allowing regeneration or not. We discuss the validity of the approximation of neglecting the {nu}{sub {tau}} regeneration using different scenarios for the neutrino-nucleon cross sections and the tau energy losses.

  12. Passive Immunization with Phospho-Tau Antibodies Reduces Tau Pathology and Functional Deficits in Two Distinct Mouse Tauopathy Models

    PubMed Central

    Sankaranarayanan, Sethu; Barten, Donna M.; Vana, Laurel; Devidze, Nino; Yang, Ling; Cadelina, Gregory; Hoque, Nina; DeCarr, Lynn; Keenan, Stefanie; Lin, Alan; Cao, Yang; Snyder, Bradley; Zhang, Bin; Nitla, Magdalena; Hirschfeld, Gregg; Barrezueta, Nestor; Polson, Craig; Wes, Paul; Rangan, Vangipuram S.; Cacace, Angela; Albright, Charles F.; Meredith, Jere; Trojanowski, John Q.; Lee, Virginia M-Y.; Brunden, Kurt R.; Ahlijanian, Michael

    2015-01-01

    In Alzheimer’s disease (AD), an extensive accumulation of extracellular amyloid plaques and intraneuronal tau tangles, along with neuronal loss, is evident in distinct brain regions. Staging of tau pathology by postmortem analysis of AD subjects suggests a sequence of initiation and subsequent spread of neurofibrillary tau tangles along defined brain anatomical pathways. Further, the severity of cognitive deficits correlates with the degree and extent of tau pathology. In this study, we demonstrate that phospho-tau (p-tau) antibodies, PHF6 and PHF13, can prevent the induction of tau pathology in primary neuron cultures. The impact of passive immunotherapy on the formation and spread of tau pathology, as well as functional deficits, was subsequently evaluated with these antibodies in two distinct transgenic mouse tauopathy models. The rTg4510 transgenic mouse is characterized by inducible over-expression of P301L mutant tau, and exhibits robust age-dependent brain tau pathology. Systemic treatment with PHF6 and PHF13 from 3 to 6 months of age led to a significant decline in brain and CSF p-tau levels. In a second model, injection of preformed tau fibrils (PFFs) comprised of recombinant tau protein encompassing the microtubule-repeat domains into the cortex and hippocampus of young P301S mutant tau over-expressing mice (PS19) led to robust tau pathology on the ipsilateral side with evidence of spread to distant sites, including the contralateral hippocampus and bilateral entorhinal cortex 4 weeks post-injection. Systemic treatment with PHF13 led to a significant decline in the spread of tau pathology in this model. The reduction in tau species after p-tau antibody treatment was associated with an improvement in novel-object recognition memory test in both models. These studies provide evidence supporting the use of tau immunotherapy as a potential treatment option for AD and other tauopathies. PMID:25933020

  13. Passive immunization with phospho-tau antibodies reduces tau pathology and functional deficits in two distinct mouse tauopathy models.

    PubMed

    Sankaranarayanan, Sethu; Barten, Donna M; Vana, Laurel; Devidze, Nino; Yang, Ling; Cadelina, Gregory; Hoque, Nina; DeCarr, Lynn; Keenan, Stefanie; Lin, Alan; Cao, Yang; Snyder, Bradley; Zhang, Bin; Nitla, Magdalena; Hirschfeld, Gregg; Barrezueta, Nestor; Polson, Craig; Wes, Paul; Rangan, Vangipuram S; Cacace, Angela; Albright, Charles F; Meredith, Jere; Trojanowski, John Q; Lee, Virginia M-Y; Brunden, Kurt R; Ahlijanian, Michael

    2015-01-01

    In Alzheimer's disease (AD), an extensive accumulation of extracellular amyloid plaques and intraneuronal tau tangles, along with neuronal loss, is evident in distinct brain regions. Staging of tau pathology by postmortem analysis of AD subjects suggests a sequence of initiation and subsequent spread of neurofibrillary tau tangles along defined brain anatomical pathways. Further, the severity of cognitive deficits correlates with the degree and extent of tau pathology. In this study, we demonstrate that phospho-tau (p-tau) antibodies, PHF6 and PHF13, can prevent the induction of tau pathology in primary neuron cultures. The impact of passive immunotherapy on the formation and spread of tau pathology, as well as functional deficits, was subsequently evaluated with these antibodies in two distinct transgenic mouse tauopathy models. The rTg4510 transgenic mouse is characterized by inducible over-expression of P301L mutant tau, and exhibits robust age-dependent brain tau pathology. Systemic treatment with PHF6 and PHF13 from 3 to 6 months of age led to a significant decline in brain and CSF p-tau levels. In a second model, injection of preformed tau fibrils (PFFs) comprised of recombinant tau protein encompassing the microtubule-repeat domains into the cortex and hippocampus of young P301S mutant tau over-expressing mice (PS19) led to robust tau pathology on the ipsilateral side with evidence of spread to distant sites, including the contralateral hippocampus and bilateral entorhinal cortex 4 weeks post-injection. Systemic treatment with PHF13 led to a significant decline in the spread of tau pathology in this model. The reduction in tau species after p-tau antibody treatment was associated with an improvement in novel-object recognition memory test in both models. These studies provide evidence supporting the use of tau immunotherapy as a potential treatment option for AD and other tauopathies.

  14. 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.

  15. 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

  16. 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.

  17. 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

  18. Horizontal Tau air showers from mountains in deep vally :Traces of Ultrahigh neutrino tau

    NASA Astrophysics Data System (ADS)

    Fargion, Daniele

    1999-08-01

    Ultra High Energy (UHE) Tau neutrino may lead to a very peculiar imprint in future underground K m3 detectors in water and ice as well as in air: rarest secondary tau tracks and decay which may exceed the muon ones. Indeed Bremsstrahlung at high energy lead to longer tracks for heavier leptons. Radiation lenght grows nearly with the square of the lepton mass. Indeed electrons are too light and their trace in matter is negligible (decimeters) muon are much better observed, while tau are too short life time and short range to be found. However, because relativistic time expansion, UHE tau traces in matter, above 1017 eV , are relativistically boosted overcoming the corresponding muon tracks, already bounded by bremsstrahlung logaritmic regime. The tau crossing for Kms in water or ice may be confused with common muon tracks; their tau decay may be missunderstood as muonic catastrophic brehmstrallung interactions. To economize UHE tau dicovery, we suggest to look the tau decay in air into the deep valleys montains, like Canyons or deep in escavation mines where horizontal air showers induce fluoresce or Cerenkov lights. The mountain valley width screens from horizontal secondary muons. The valley height increases the solid angle view. The horizontal air Kms-size gap offer a strong discriminator to filter UHE muons against tau. Tens event a year at PeV ( W resonance peak) energies in K m3 excavation gap should be observable . Hunting air shower in the night toward high mountains in Canyons or in a deep excavation may be the best and cheapest way to discover UHE neutrinos , either born by electron antineutrino scattering on electrons at PeV energies, or by direct tau neutrino possibly relic of muonic flavour oscillation even at EeV energies.

  19. Study of {tau}{sup -}{yields}VP{sup -}{nu}{sub {tau}} in the framework of resonance chiral theory

    SciTech Connect

    Guo Zhihui

    2008-08-01

    In this paper we study two kinds of {tau} decays: (a) {tau}{sup -}{yields}({rho}{sup 0}{pi}{sup -},{omega}{pi}{sup -},{phi}{pi}{sup -},K*{sup 0}K{sup -}){nu}{sub {tau}}, which belong to {delta}S=0 processes and (b) {delta}S=1 processes, such as {tau}{sup -}{yields}({rho}{sup 0}K{sup -},{omega}K{sup -},{phi}K{sup -},K*{sup 0}{pi}{sup -}){nu}{sub {tau}}, in the framework of resonance chiral theory (R{chi}T). We fit the {tau}{sup -}{yields}{omega}{pi}{sup -}{nu}{sub {tau}} spectral function and the invariant mass distribution of {omega}K in the process of {tau}{sup -}{yields}{omega}K{sup -}{nu}{sub {tau}} to get the values of unknown resonance couplings. Then we make a prediction for branching ratios of all channels.

  20. 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

  1. Modulation of tau protein fibrillization by oleocanthal.

    PubMed

    Monti, Maria Chiara; Margarucci, Luigi; Riccio, Raffaele; Casapullo, Agostino

    2012-09-28

    Among the phenolic compounds extracted from extra virgin olive oil, oleocanthal (1) has attracted considerable attention in the modulation of many human diseases, such as inflammation and Alzheimer's disease (AD). Indeed, 1 is capable of altering the fibrillization of tau protein, which is one of the key factors at the basis of neurodegenerative diseases, and of covalently reacting with lysine ε-amino groups of the tau fragment K18 in an unspecific fashion. In the present study, an investigation of the recognition process and the reaction profile between 1 and the wild-type tau protein has been conducted by a circular dichroism, surface plasmon resonance, fluorescence, and mass spectrometry combined approach. As a result, 1 has been found to interact with tau-441, inducing stable conformational modifications of the protein secondary structure and also interfering with tau aggregation. These findings provide experimental support for the potential reduced risk of AD and related neurodegenerative diseases associated with olive oil consumption and may offer a new chemical scaffold for the development of AD-modulating agents. PMID:22988908

  2. 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.

  3. Nuclear and cytoplasmic tau proteins from human nonneuronal cells share common structural and functional features with brain tau.

    PubMed

    Cross, D C; Muñoz, J P; Hernández, P; Maccioni, R B

    2000-05-01

    The heterogeneous family of tau proteins interacts with microtubules, actin filaments, and intermediate filaments. The tau isoforms have been shown to play a major role in neuronal polarity. However, tau-like proteins have been found in several other types of cells. Previous studies have also indicated the presence of a nuclear tau. The relationships between nuclear and cytoplasmic tau as well as the functional aspects of the nuclear tau are unknown. In this study, we demonstrate by reverse transcriptase polymerase chain reaction using specific primers that a transcript with features of neuronal tau is present in human fibroblast and Huh-7 hepatoma cell lines. Additionally, we present the first isolation and characterization of cytosolic and nuclear tau-like proteins from nonneuronal cells. Nonneuronal cytosolic tau components were isolated using the perchloric acid precipitation approach, while nuclear tau was isolated after selective extractions using high-ionic strength buffers. The cytoplasmic tau of nonneuronal cells is composed of at least three isoforms, whereas two main isoforms were detected in nuclear tau. Interestingly, the cytoplasmic and nuclear tau components exhibited the capacity to promote tubulin polymerization in vitro. Immunofluorescence studies using monoclonal anti-tau antibodies indicated a discrete distribution of tau protein in both the interphase and mitotic nucleus. In the latter, tau colocalized with the chromosomal scaffold. These studies, together with previous evidence on tau roles in modulating microtubule growth from centrosomes, and its role in the interaction patterns that stabilize the integrity of the cytoskeletal network, strongly support the idea that tau is a multifunctional protein involved in fundamental cellular processes. PMID:10842324

  4. 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.

  5. 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).

  6. Aminothienopyridazines and Methylene Blue Affect Tau Fibrillization via Cysteine Oxidation*

    PubMed Central

    Crowe, Alex; James, Michael J.; Lee, Virginia M.-Y.; Smith, Amos B.; Trojanowski, John Q.; Ballatore, Carlo; Brunden, Kurt R.

    2013-01-01

    Alzheimer disease and several other neurodegenerative disorders are characterized by the accumulation of intraneuronal fibrils comprised of the protein Tau. Tau is normally a soluble protein that stabilizes microtubules, with splice isoforms that contain either three (3-R) or four (4-R) microtubule binding repeats. The formation of Tau fibrils is thought to result in neuronal damage, and inhibitors of Tau fibrillization may hold promise as therapeutic agents. The process of Tau fibrillization can be replicated in vitro, and a number of small molecules have been identified that inhibit Tau fibril formation. However, little is known about how these molecules affect Tau fibrillization. Here, we examined the mechanism by which the previously described aminothieno pyridazine (ATPZ) series of compounds inhibit Tau fibrillization. Active ATPZs were found to promote the oxidation of the two cysteine residues within 4-R Tau by a redox cycling mechanism, resulting in the formation of a disulfide-containing compact monomer that was refractory to fibrillization. Moreover, the ATPZs facilitated intermolecular disulfide formation between 3-R Tau monomers, leading to dimers that were capable of fibrillization. The ATPZs also caused cysteine oxidation in molecules unrelated to Tau. Interestingly, methylene blue, an inhibitor of Tau fibrillization under evaluation in Alzheimer disease clinical trials, caused a similar oxidation of cysteines in Tau and other molecules. These findings reveal that the ATPZs and methylene blue act by a mechanism that may affect their viability as potential therapeutic agents. PMID:23443659

  7. Studies of {tau}{sup -}{yields}{eta}K{sup -}{nu}{sub {tau}} and {tau}{sup -}{yields}{eta}{pi}{sup -}{nu}{sub {tau}} at BABAR and a search for a second-class current

    SciTech Connect

    Amo Sanchez, P. del; Lees, J. P.; Poireau, V.; Prencipe, E.; Tisserand, V.; Martinelli, M.; Palano, A.; Pappagallo, M.; Eigen, G.; Stugu, B.; Sun, L.; Battaglia, M.; Brown, D. N.; Hooberman, B.; Kerth, L. T.; Kolomensky, Yu. G.; Lynch, G.; Osipenkov, I. L.

    2011-02-01

    We report on analyses of tau lepton decays {tau}{sup -}{yields}{eta}K{sup -}{nu}{sub {tau}} and {tau}{sup -}{yields}{eta}{pi}{sup -}{nu}{sub {tau}}, with {eta}{yields}{pi}{sup +}{pi}{sup -}{pi}{sup 0}, using 470 fb{sup -1} of data from the BABAR experiment at PEP-II, collected at center-of-mass energies at and near the {Upsilon}(4S) resonance. We measure the branching fraction for the {tau}{sup -}{yields}{eta}K{sup -}{nu}{sub {tau}} decay mode, B({tau}{sup -}{yields}{eta}K{sup -}{nu}{sub {tau}})=(1.42{+-}0.11(stat){+-}0.07(syst))x10{sup -4}, and report a 95% confidence level upper limit for the second-class current process {tau}{sup -}{yields}{eta}{pi}{sup -}{nu}{sub {tau}}, B({tau}{sup -}{yields}{eta}{pi}{sup -}{nu}{sub {tau}})<9.9x10{sup -5}.

  8. 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.

  9. Inhibition of tau fibrillization by oleocanthal via reaction with the amino groups of tau.

    PubMed

    Li, Wenkai; Sperry, Jeffrey B; Crowe, Alex; Trojanowski, John Q; Smith, Amos B; Lee, Virginia M-Y

    2009-08-01

    Tau is a microtubule-associated protein that promotes microtubule assembly and stability. In Alzheimer's disease and related tauopathies, tau fibrillizes and aggregates into neurofibrillary tangles. Recently, oleocanthal isolated from extra virgin olive oil was found to display non-steroidal anti-inflammatory activity similar to ibuprofen. As our unpublished data indicates an inhibitory effect of oleocanthal on amyloid beta peptide fibrillization, we reasoned that it might inhibit tau fibrillization as well. Herein, we demonstrate that oleocanthal abrogates fibrillization of tau by locking tau into the naturally unfolded state. Using PHF6 consisting of the amino acid residues VQIVYK, a hexapeptide within the third repeat of tau that is essential for fibrillization, we show that oleocanthal forms an adduct with the lysine via initial Schiff base formation. Structure and function studies demonstrate that the two aldehyde groups of oleocanthal are required for the inhibitory activity. These two aldehyde groups show certain specificity when titrated with free lysine and oleocanthal does not significantly affect the normal function of tau. These findings provide a potential scheme for the development of novel therapies for neurodegenerative tauopathies. PMID:19549281

  10. Search for new physics in B{yields}D*{tau}nu-bar {sub {tau}} decay

    SciTech Connect

    Fajfer, Svjetlana; Kamenik, Jernej F.; Nisandzic, Ivan

    2012-10-23

    B physics offers important tests of the Standard Model at low energies. Recently, BaBar observed significant deviations from the Standard Model expectations in the semileptonic B{yields}D{sup (*)}{tau}{nu}{sub {tau}} decays. Interestingly, the measured leptonic B{yields}{tau}{nu} branching fraction also deviates from CKM unitarity predictions. Motivated by these results we investigate the most general set of lowest dimensional effective operators leading to modifications of b{yields}c(u) (semi)tauonic transitions. Allowing for general flavor violation, we find that among possible operator structures, new contributions from right-right vector and right-left scalar quark currents provide viable explanations of the anomalies. In addition, we identify a number of B{yields}D*{tau}{nu}{sub {tau}} transition observables with the power to discriminate among the various effective operators' contributions. They are the differential decay rate, longitudinal D* polarization fraction, D*-{tau} opening angle asymmetry and the {tau} helicity asymmetry.

  11. Tau kinase inhibitors protect hippocampal synapses despite of insoluble tau accumulation.

    PubMed

    Hinners, Ina; Hill, Anika; Otto, Ulrike; Michalsky, Anke; Mack, Till G A; Striggow, Frank

    2008-03-01

    A better understanding of the cellular and molecular pathomechanisms of Alzheimer's disease (AD) is a prerequisite for the development of efficient treatments. We have used a novel assay system based on virus-transduced organotypic hippocampal slice cultures that mimics important aspects of tau-driven AD pathology in a short time frame. Human tau P301L, when expressed in pyramidal neurons of hippocampal slice cultures, was increasingly phosphorylated at several disease-relevant epitopes, leading to progressive neuronal dystrophy and formation of RIPA-insoluble tau. AD-like tau hyperphosphorylation was reduced by the tau kinase inhibitors lithium and SRN-003-556, but RIPA-insoluble tau remained unaffected after treatment with any of these substances. Only SRN-003-556 was able to protect hippocampal neurons from synaptic damage that was presumably caused by a toxic soluble tau fraction. These data provide first mechanistic insights towards the functional benefits of SRN-003-556 that have been observed in vivo.

  12. Inhibition of tau fibrillization by oleocanthal via reaction with the amino groups of tau

    PubMed Central

    Li, Wenkai; Sperry, Jeffrey B.; Crowe, Alex; Trojanowski, John Q.; Smith, Amos B.; Lee, Virginia M.-Y.

    2009-01-01

    Tau is a microtubule-associated protein that promotes microtubule assembly and stability. In Alzheimer's disease and related tauopathies, tau fibrillizes and aggregates into neurofibrillary tangles. Recently, oleocanthal isolated from extra virgin olive oil was found to display non-steroidal anti-inflammatory activity similar to ibuprofen. Since our unpublished data indicates an inhibitory effect of oleocanthal on Aβ fibrillization, we reasoned that it might inhibit tau fibrillization as well. Herein we demonstrate that oleocanthal abrogates fibrillization of tau by locking tau into the naturally unfolded state. Using PHF6 consisting of the amino acid residues VQIVYK, a hexapeptide within the third repeat of tau that is essential for fibrillization, we show that oleocanthal forms an adduct with the lysine via initial Schiff base formation. Structure and function studies demonstrate that the two aldehyde groups of oleocanthal are required for the inhibitory activity. These two aldehyde groups show certain specificity when titrated with free lysine and oleocanthal does not significantly affect the normal function of tau. These findings provide a potential scheme for the development of novel therapies for neurodegenerative tauopathies. PMID:19549281

  13. 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.

  14. Structural determinants of Tau aggregation inhibitor potency.

    PubMed

    Schafer, Kelsey N; Cisek, Katryna; Huseby, Carol J; Chang, Edward; Kuret, Jeff

    2013-11-01

    Small-molecule Tau aggregation inhibitors are under investigation as potential therapeutic agents against Alzheimer disease. Many such inhibitors have been identified in vitro, but their potency-driving features, and their molecular targets in the Tau aggregation pathway, have resisted identification. Previously we proposed ligand polarizability, a measure of electron delocalization, as a candidate descriptor of inhibitor potency. Here we tested this hypothesis by correlating the ground state polarizabilities of cyanine, phenothiazine, and arylmethine derivatives calculated using ab initio quantum methods with inhibitory potency values determined in the presence of octadecyl sulfate inducer under reducing conditions. A series of rhodanine analogs was analyzed as well using potency values disclosed in the literature. Results showed that polarizability and inhibitory potency directly correlated within all four series. To identify putative binding targets, representative members of the four chemotypes were added to aggregation reactions, where they were found to stabilize soluble, but SDS-resistant Tau species at the expense of filamentous aggregates. Using SDS resistance as a secondary assay, and a library of Tau deletion and missense mutants as targets, interaction with cyanine was localized to the microtubule binding repeat region. Moreover, the SDS-resistant phenotype was completely dependent on the presence of octadecyl sulfate inducer, but not intact PHF6/PH6* hexapeptide motifs, indicating that cyanine interacted with a species in the aggregation pathway prior to nucleus formation. Together the data suggest that flat, highly polarizable ligands inhibit Tau aggregation by interacting with folded species in the aggregation pathway and driving their assembly into soluble but highly stable Tau oligomers.

  15. Structural Determinants of Tau Aggregation Inhibitor Potency*

    PubMed Central

    Schafer, Kelsey N.; Cisek, Katryna; Huseby, Carol J.; Chang, Edward; Kuret, Jeff

    2013-01-01

    Small-molecule Tau aggregation inhibitors are under investigation as potential therapeutic agents against Alzheimer disease. Many such inhibitors have been identified in vitro, but their potency-driving features, and their molecular targets in the Tau aggregation pathway, have resisted identification. Previously we proposed ligand polarizability, a measure of electron delocalization, as a candidate descriptor of inhibitor potency. Here we tested this hypothesis by correlating the ground state polarizabilities of cyanine, phenothiazine, and arylmethine derivatives calculated using ab initio quantum methods with inhibitory potency values determined in the presence of octadecyl sulfate inducer under reducing conditions. A series of rhodanine analogs was analyzed as well using potency values disclosed in the literature. Results showed that polarizability and inhibitory potency directly correlated within all four series. To identify putative binding targets, representative members of the four chemotypes were added to aggregation reactions, where they were found to stabilize soluble, but SDS-resistant Tau species at the expense of filamentous aggregates. Using SDS resistance as a secondary assay, and a library of Tau deletion and missense mutants as targets, interaction with cyanine was localized to the microtubule binding repeat region. Moreover, the SDS-resistant phenotype was completely dependent on the presence of octadecyl sulfate inducer, but not intact PHF6/PH6* hexapeptide motifs, indicating that cyanine interacted with a species in the aggregation pathway prior to nucleus formation. Together the data suggest that flat, highly polarizable ligands inhibit Tau aggregation by interacting with folded species in the aggregation pathway and driving their assembly into soluble but highly stable Tau oligomers. PMID:24072703

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

    PubMed Central

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

    2013-01-01

    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

  17. B Meson Decays With Tau Leptons in the Final State

    SciTech Connect

    Mazur, Michael; /Freiburg U.

    2009-08-05

    We present measurements of B meson decays with {tau} leptons in the final state. These decays, while experimentally more challenging than those involving light leptons, provide enhanced sensitivity to physics beyond the Standard Model due to the large {tau} mass. We present measurements of the branching fractions of B{sup -} {yields} {tau}{sup -} {bar {nu}}{sub {tau}} and B {yields} D{sup (*)}{tau}{sup -}{bar {nu}}{sub {tau}}, as well as searches for the forbidden decays B{sup 0} {yields} {ell}{sup {+-}}{tau}{sup {-+}} and B{sup -} {yields} K{sup -} {tau}{sup {+-}}{mu}{sup {-+}}. These measurements are based on several hundred million e{sup +}e{sup -} {yields} {Upsilon}(4S) {yields} B{bar B} events recorded with the BaBar detector at the PEP-II asymmetric-energy collider.

  18. Atmospheric tau neutrinos in a multikiloton liquid argon detector

    SciTech Connect

    Conrad, Janet; Gouvea, Andre de; Shalgar, Shashank; Spitz, Joshua

    2010-11-01

    An ultralarge liquid argon time projection chamber based neutrino detector will have the uncommon ability to detect atmospheric {nu}{sub {tau}}/{nu}{tau} events. This paper discusses the most promising modes for identifying charged current {nu}{sub {tau}}/{nu}{tau}, and shows that, with simple kinematic cuts, {approx}30 {nu}{sub {tau}}+{nu}{tau} interactions can be isolated in a 100 kt{center_dot}yr exposure, with greater than 4{sigma} significance. This sample is sufficient to perform flux-averaged total cross-section and cross-section shape parametrization measurements--the first steps toward using {nu}{sub {tau}}/{nu}{tau} to search for physics beyond the standard model.

  19. Synaptic Contacts Enhance Cell-to-Cell Tau Pathology Propagation.

    PubMed

    Calafate, Sara; Buist, Arjan; Miskiewicz, Katarzyna; Vijayan, Vinoy; Daneels, Guy; de Strooper, Bart; de Wit, Joris; Verstreken, Patrik; Moechars, Diederik

    2015-05-26

    Accumulation of insoluble Tau protein aggregates and stereotypical propagation of Tau pathology through the brain are common hallmarks of tauopathies, including Alzheimer's disease (AD). Propagation of Tau pathology appears to occur along connected neurons, but whether synaptic contacts between neurons are facilitating propagation has not been demonstrated. Using quantitative in vitro models, we demonstrate that, in parallel to non-synaptic mechanisms, synapses, but not merely the close distance between the cells, enhance the propagation of Tau pathology between acceptor hippocampal neurons and Tau donor cells. Similarly, in an artificial neuronal network using microfluidic devices, synapses and synaptic activity are promoting neuronal Tau pathology propagation in parallel to the non-synaptic mechanisms. Our work indicates that the physical presence of synaptic contacts between neurons facilitate Tau pathology propagation. These findings can have implications for synaptic repair therapies, which may turn out to have adverse effects by promoting propagation of Tau pathology.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. Dielectric relaxation of alpha -tocopherol acetate (vitamin E).

    PubMed

    Kaminski, K; Maslanka, S; Ziolo, J; Paluch, M; McGrath, K J; Roland, C M

    2007-01-01

    Dielectric loss spectra are reported for alpha -tocopherol acetate (an isomer of vitamin E) in the supercooled and glassy states. The alpha -relaxation times, tau_{alpha} , measured over a 190 degrees range of temperatures, T , at pressures, P , up to 400MPa can be expressed as a single function of TV3.9 ( V is specific volume, measured herein as a function of T and P ). At ambient pressure, there is no dynamic crossover over eight decades of measured tau_{alpha} . The relaxation spectra above the glass transition temperature T_{g} show ionic conductivity and an excess wing on the high-frequency flank of the alpha -relaxation loss peak. Temperature-pressure superpositioning is valid for the alpha process; moreover, the peak shape is constant (stretch exponent equal to 0.65). However, application of pressure changes the shape of the dielectric spectrum at higher frequencies due to the shift of the excess wing to form a resolved peak. Additionally, another relaxation process, absent at atmospheric pressure, emerges on the high-frequency side of the alpha -process. We propose that this new peak reflects a more compact conformation of the alpha -tocopherol acetate molecule. Drawing on the coupling model, the experimentally determined relaxation times, activation energy, and activation volume for the Johari-Goldstein process are compared to values calculated from the properties of the alpha relaxation. The agreement is generally satisfactory, at least for T

  7. Teaching science through inquiry in K--5 classrooms: Analysis of change in practice

    NASA Astrophysics Data System (ADS)

    Sciulli, Joseph A.

    The purpose of this study was to examine the role professional development takes in fostering change in the pedagogical practices of K--5 classroom teachers, specifically in teaching science through inquiry. Michael Fullan's three elements essential for change: curriculum, instruction, and philosophy, were used as the lens through which to observe and analyze the impact of an intervention for changing teaching practices in K--5 classrooms. The intervention that assisted in creating an environment for change in behaviors was a morphed version of the Exploratorium's Institute for Inquiry, the ASSET Institute for Inquiry, in Pittsburgh, Pennsylvania. During a three year period 208 teachers attended the five day Institute. It modeled the pedagogy, philosophy and related curriculum strategies indigenous to teaching science through inquiry. Each teacher was sent a questionnaire. The questionnaire was a compilation of Horizon Research, National Science Education Standards, and the National Science Education Inquiry Standard. The analysis of the statistical relationships between the Institute and change in the use of curriculum, instruction, or beliefs in action was done. The results indicate a statistically significant relationship between the Institute for Inquiry and change in teaching practices. There was an increase in the use and implementation of hands-on inquiry-based curricula: STC, FOSS, and INSIGHTS. There was an increase in those instructional strategies and classroom practices supportive of science through inquiry. There was a statistical relationship between the intervention and the NSES indicators of inquiry in practice. Further research was done with regard to teaching experience (i.e., number of years teaching), time interval between completion of the intervention and implementation of the philosophy and strategies indigenous to inquiry, and the relationship a resource teacher (e.g., teacher teaching teacher) develops with classroom teachers and the

  8. 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))%.

  9. Enumerative Geometry, Tau-Functions and Heisenberg-Virasoro Algebra

    NASA Astrophysics Data System (ADS)

    Alexandrov, A.

    2015-08-01

    In this paper we establish relations between three enumerative geometry tau-functions, namely the Kontsevich-Witten, Hurwitz and Hodge tau-functions. The relations allow us to describe the tau-functions in terms of matrix integrals, Virasoro constraints and Kac-Schwarz operators. All constructed operators belong to the algebra (or group) of symmetries of the KP hierarchy.

  10. 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.

  11. 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

  12. 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

  13. Evidence of the purely leptonic decay B- --> tau- nu(tau).

    PubMed

    Ikado, K; Abe, K; Abe, K; Adachi, I; Aihara, H; Akai, K; Akemoto, M; Anipko, D; Arinstein, K; Aulchenko, V; Aushev, T; Aziz, T; Bakich, A M; Balagura, V; Barbero, M; Bay, A; Bedny, I; Belous, K; Bitenc, U; Bizjak, I; Bondar, A; Bozek, A; Bracko, M; Browder, T E; Chang, P; Chen, A; Chen, W T; Choi, Y; Cole, S; Dalseno, J; Danilov, M; Dash, M; Eidelman, S; Epifanov, D; Flanagan, J; Fratina, S; Furukawa, K; Gabyshev, N; Gershon, T; Go, A; Gokhroo, G; Golob, B; Gorisek, A; Ha, H; Haba, J; Hara, K; Hara, T; Hastings, N C; Hayasaka, K; Hayashii, H; Hazumi, M; Hinz, L; Hokuue, T; Hoshi, Y; Hou, S; Hou, W-S; Iida, N; Iijima, T; Imoto, A; Inami, K; Ishikawa, A; Ishino, H; Itoh, R; Iwasaki, M; Iwasaki, Y; Kamitani, T; Kang, J H; Kataoka, S U; Katayama, N; Kawai, H; Kawasaki, T; Kichimi, H; Kikutani, E; Kim, H J; Kim, H O; Kinoshita, K; Koiso, H; Korpar, S; Krizan, P; Krokovny, P; Kulasiri, R; Kumar, R; Kuo, C C; Kuzmin, A; Kwon, Y-J; Lange, J S; Leder, G; Lee, J; Lesiak, T; Limosani, A; Lin, S-W; Liventsev, D; Marlow, D; Matsumoto, T; Matyja, A; McOnie, S; Michizono, S; Mimashi, T; Mitaroff, W; Miyabayashi, K; Miyata, H; Miyazaki, Y; Mizuk, R; Nagamine, T; Nakamura, I; Nakamura, T T; Nakano, E; Nakao, M; Nishida, S; Nitoh, O; Noguchi, S; Nozaki, T; Ogawa, S; Ogawa, Y; Ohmi, K; Ohshima, T; Ohuchi, N; Oide, K; Okabe, T; Okuno, S; Olsen, S L; Onuki, Y; Ostrowicz, W; Ozaki, H; Pakhlov, P; Park, C W; Park, H; Pestotnik, R; Piilonen, L E; Poluektov, A; Rozanska, M; Sakai, Y; Schietinger, T; Schneider, O; Schwanda, C; Senyo, K; Sevior, M E; Shapkin, M; Shibuya, H; Shidara, T; Shwartz, B; Sidorov, V; Sokolov, A; Somov, A; Stanic, S; Staric, M; Stoeck, H; Sumisawa, K; Sumiyoshi, T; Suzuki, S; Tajima, O; Takasaki, F; Tamai, K; Tamura, N; Tanaka, M; Tawada, M; Taylor, G N; Teramoto, Y; Tian, X C; Trabelsi, K; Tsuboyama, T; Tsukamoto, T; Uehara, S; Uglov, T; Ueno, K; Unno, Y; Uno, S; Usov, Y; Varner, G; Villa, S; Wang, C C; Wang, C H; Watanabe, Y; Won, E; Yabsley, B D; Yamaguchi, A; Yamashita, Y; Yamauchi, M; Yoshida, M; Yusa, Y; Zhang, L M; Zhang, Z P; Zhilich, V; Zürcher, D

    2006-12-22

    We present the first evidence of the decay B- --> tau- nu(tau), using 414 fb(-1) of data collected at the Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric-energy e+ e- collider. Events are tagged by fully reconstructing one of the B mesons in hadronic modes. We detect the signal with a significance of 3.5 standard deviations including systematics and measure the branching fraction to be B(B- --> tau- nu(tau)) = (1.79(-0.49) +0.56(stat)(-0.51) +0.46(syst)) x 10(-4). This implies that fB = 0.229(-0.031) +0.036(stat)(-0.037) +0.034(syst) GeV and is the first direct measurement of this quantity. PMID:17280341

  14. KEY COMPARISON: CCL-K5: CMM 1D: Step gauge and ball bars: Final report

    NASA Astrophysics Data System (ADS)

    Jusko, Otto; Brown, Nicholas; Thalmann, Rudolf; Arizmendi Reyes, Edgar; Phillips, Steven; Eom, Cheon Il; Shaoxi, Shen; Takatsuji, Toshiyuki; Prieto, Emilio

    2006-01-01

    The results of the CCL key comparison on the calibration of a step gauge and ball bars are reported (CCL-K5). Nine NMIs participated in the comparison. The measured artifacts were a step gauge of 1000 mm length and three ball bars: two made from steel (400 mm and 800 mm in length) and one from Super Invar (800 mm long). The Key Comparison Reference Value (KCRV) for the step gauge was the mean of four laboratories, and the mean of all participants for the ball bars. The data for the step gauge have been analysed into constant and proportional components to reduce the quantity of data and separate out the random variation in measurements from proportional errors which generally have a different cause. All participating NMIs measured the step gauge and were generally in good agreement. Some results revealed problems with this measurement, and as such, helped to improve the measurement procedures of these NMIs for the future. Only a few NMIs delivered data for the ball bars and these results were in good agreement. 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 CCL, according to the provisions of the CIPM Mutual Recognition Arrangement (MRA).

  15. Tau Lepton Flavor Violation Results from BABAR

    NASA Astrophysics Data System (ADS)

    Cervelli, A.

    2009-12-01

    We report the recent results obtained by BABAR collaboration in lepton flavor violation (LFV) searches in the tau lepton sector, presenting 16 new results from τLLL (L = e, μ), τ→LV0 (V0 = ρ0, K*0, K*-0, Φ and τ→LKS.

  16. Tau Phosphorylation, Aggregation, and Cell Toxicity

    PubMed Central

    Avila, J.; Santa-María, I.; Pérez, M.; Hernández, F.; Moreno, F.

    2006-01-01

    Protein aggregation takes place in many neurodegenerative disorders. However, there is a controversy about the possible toxicity of these protein aggregates. In this review, this controversy is discussed, focussing on the tau aggregation that takes place in those disorders known as tauopathies. PMID:17047313

  17. 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%.

  18. 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

  19. Measurement of the Semileptonic Anti-B to D(*) Tau Anti-Nu/Tau Decays at BaBar

    SciTech Connect

    Lopes Pegna, David; /Princeton U.

    2011-11-11

    Semileptonic B meson decays into final states containing the {tau} lepton are of interesting as they provide information on the Standard Model as well as a window on new physics effects. We present results on {bar B} {yields} D{sup (*)} {tau}{bar {nu}}{sub {tau}} decays where the second B in the event is fully reconstructed.

  20. 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.

  1. Review of recent results on the /tau/ lepton

    SciTech Connect

    Gan, K.K.

    1988-04-01

    This is a review of the recent results on the /tau/ lepton. The results include precise measurements of the lifetime, measurements of the decay /tau//sup /minus// ..-->.. ..pi../sup /minus//2..pi../sup 0/..nu../sub /tau// with much improved precision, limits on decay modes containing /eta/ mesons, including the second-class-current decay /tau//sup /minus// ..-->.. ..pi../sup /minus///eta/..nu../sub /tau//, and limits on exotic decay modes. The implications of these results on the discrepancy in the one-charged-particle decay modes are discussed. 43 refs., 4 figs., 2 tabs.

  2. Discodermolide interferes with the binding of tau protein to microtubules.

    PubMed

    Kar, Santwana; Florence, Gordon J; Paterson, Ian; Amos, Linda A

    2003-03-27

    We investigated whether discodermolide, a novel antimitotic agent, affects the binding to microtubules of tau protein repeat motifs. Like taxol, the new drug reduces the proportion of tau that pellets with microtubules. Despite their differing structures, discodermolide, taxol and tau repeats all bind to a site on beta-tubulin that lies within the microtubule lumen and is crucial in controlling microtubule assembly. Low concentrations of tau still bind strongly to the outer surfaces of preformed microtubules when the acidic C-terminal regions of at least six tubulin dimers are available for interaction with each tau molecule; otherwise binding is very weak.

  3. 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

  4. 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

  5. T-Tau and P-Tau in Brain and Blood from Natural and Experimental Prion Diseases.

    PubMed

    Rubenstein, Richard; Chang, Binggong; Petersen, Robert; Chiu, Allen; Davies, Peter

    2015-01-01

    Synaptic abnormalities are prominent in prion disease pathogenesis and are responsible for functional deficits. The microtubule associated protein, Tau, binds to and stabilizes microtubules in axons ensuring axonal transport of synaptic components. Tau phosphorylation reduces its affinity for microtubules leading to their instability and resulting in disrupted axonal transport and synaptic dysfunction. We report on the levels of total Tau (T-Tau) and phosphorylated Tau (P-Tau), measured by highly sensitive laser-based immunoassays, in the central nervous system and biofluids from experimentally transmitted prion disease in mice and natural cases of sporadic Creutzfeldt-Jakob Disease (sCJD) in humans. We found that, in contrast to sCJD where only the levels of T-Tau in brain are increased, both T-Tau and P-Tau are increased in the brains of symptomatic mice experimentally infected with the ME7, 139A and 22L mouse-adapted scrapie strains. The increased levels of T-Tau in sCJD brain, compared to control samples, were also observed in patient plasma. In contrast, there was no detectable increase in T-Tau and P-Tau in plasma from symptomatic experimentally infected mice. Furthermore, our data suggests that in mice showing clinical signs of prion disease the levels and/or ratios of T-Tau and P-Tau are only a useful parameter for differentiating the mouse-adapted scrapie strains that differ in the extent of disease. We conclude that the neuropathogenesis associated with P-Tau and synaptic dysfunction is similar for at least two of the mouse-adapted scrapie strains tested but may differ between sporadic and experimentally transmitted prion diseases. PMID:26630676

  6. T-Tau and P-Tau in Brain and Blood from Natural and Experimental Prion Diseases

    PubMed Central

    Rubenstein, Richard; Chang, Binggong; Petersen, Robert; Chiu, Allen; Davies, Peter

    2015-01-01

    Synaptic abnormalities are prominent in prion disease pathogenesis and are responsible for functional deficits. The microtubule associated protein, Tau, binds to and stabilizes microtubules in axons ensuring axonal transport of synaptic components. Tau phosphorylation reduces its affinity for microtubules leading to their instability and resulting in disrupted axonal transport and synaptic dysfunction. We report on the levels of total Tau (T-Tau) and phosphorylated Tau (P-Tau), measured by highly sensitive laser-based immunoassays, in the central nervous system and biofluids from experimentally transmitted prion disease in mice and natural cases of sporadic Creutzfeldt-Jakob Disease (sCJD) in humans. We found that, in contrast to sCJD where only the levels of T-Tau in brain are increased, both T-Tau and P-Tau are increased in the brains of symptomatic mice experimentally infected with the ME7, 139A and 22L mouse-adapted scrapie strains. The increased levels of T-Tau in sCJD brain, compared to control samples, were also observed in patient plasma. In contrast, there was no detectable increase in T-Tau and P-Tau in plasma from symptomatic experimentally infected mice. Furthermore, our data suggests that in mice showing clinical signs of prion disease the levels and/or ratios of T-Tau and P-Tau are only a useful parameter for differentiating the mouse-adapted scrapie strains that differ in the extent of disease. We conclude that the neuropathogenesis associated with P-Tau and synaptic dysfunction is similar for at least two of the mouse-adapted scrapie strains tested but may differ between sporadic and experimentally transmitted prion diseases. PMID:26630676

  7. Tau mis-splicing in the pathogenesis of neurodegenerative disorders.

    PubMed

    Park, Sun Ah; Ahn, Sang Il; Gallo, Jean-Marc

    2016-08-01

    Tau proteins, which stabilize the structure and regulate the dynamics of microtubules, also play important roles in axonal transport and signal transduction. Tau proteins are missorted, aggregated, and found as tau inclusions under many pathological conditions associated with neurodegenerative disorders, which are collectively known as tauopathies. In the adult human brain, tau protein can be expressed in six isoforms due to alternative splicing. The aberrant splicing of tau pre-mRNA has been consistently identified in a variety of tauopathies but is not restricted to these types of disorders as it is also present in patients with non-tau proteinopathies and RNAopathies. Tau mis-splicing results in isoform-specific impairments in normal physiological function and enhanced recruitment of excessive tau isoforms into the pathological process. A variety of factors are involved in the complex set of mechanisms underlying tau mis-splicing, but variation in the cis-element, methylation of the MAPT gene, genetic polymorphisms, the quantity and activity of spliceosomal proteins, and the patency of other RNA-binding proteins, are related to aberrant splicing. Currently, there is a lack of appropriate therapeutic strategies aimed at correcting the tau mis-splicing process in patients with neurodegenerative disorders. Thus, a more comprehensive understanding of the relationship between tau mis-splicing and neurodegenerative disorders will aid in the development of efficient therapeutic strategies for patients with a tauopathy or other, related neurodegenerative disorders. [BMB Reports 2016; 49(8): 405-413]. PMID:27222125

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. APP Metabolism Regulates Tau Proteostasis in Human Cerebral Cortex Neurons

    PubMed Central

    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.

    2015-01-01

    Summary 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

  13. Tau Binds to Multiple Tubulin Dimers with Helical Structure.

    PubMed

    Li, Xiao-Han; Culver, Jacob A; Rhoades, Elizabeth

    2015-07-29

    Understanding the mechanism by which tau binds to and promotes microtubule (MT) assembly as part of its native function may also provide insight into its loss of function that occurs in neurodegenerative disease. Both mechanistic and structural studies of tau have been hindered by its intrinsic disorder and highly dynamic nature. Here, we combine fluorescence correlation spectroscopy and acrylodan fluorescence screening to study the stoichiometry and structural features of tau-tubulin assemblies. Our results show that tau binds to multiple tubulin dimers, even when MT assembly is inhibited. Moreover, we observe helical structure in the repeat regions of the MT binding domain of tau in the tau-tubulin complex, reflecting partial folding upon binding. Our findings support a role for tau's intrinsic disorder in providing a flexible scaffold for binding tubulin and MTs and a disorder-to-order transition in mediating this important interaction.

  14. Effects of 3-repeat tau on taxol mobility through microtubules

    NASA Astrophysics Data System (ADS)

    Park, Hyunjoo; Fygenson, Deborah; Kim, Mahn Won

    2005-03-01

    Both the anti-cancer drug taxol and the microtubule-associated protein tau suppress dynamics of microtubules (MT). We have observed taxol mobility with full-length 3-repeat tau, one of six tau isoforms, using fluorescence recovery after photobleaching (FRAP) on MTs and compare with earlier results on recombinant full-length adult 4-repeat tau. Taxol mobility becomes highly sensitive to taxol concentration in the presence of 3-repeat tau (up to 1:1 molar ratio) as it does in the presence of 4-repeat tau, but is 2 to 3 times faster at low taxol concentrations. Fitting to a mean-field binding reaction model [J.L. Ross et.al, PNAS 101:12910-5 (2004)] suggests that the presence of 3-repeat tau enhances taxol movement through pores in the MT walls.

  15. 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.

  16. The Kaposi's sarcoma-associated herpesvirus K5 E3 ubiquitin ligase modulates targets by multiple molecular mechanisms.

    PubMed

    Means, Robert E; Lang, Sabine M; Jung, Jae U

    2007-06-01

    Kaposi's sarcoma-associated herpesvirus encodes two highly related membrane-associated, RING-CH-containing (MARCH) family E3 ubiquitin ligases, K3 and K5, that can down regulate a variety of cell surface proteins through enhancement of their endocytosis and degradation. In this report we present data that while K5 modulation of major histocompatibility complex class I (MHC-I) closely mirrors the mechanisms used by K3, alternative molecular pathways are utilized by this E3 ligase in the down regulation of intercellular adhesion molecule 1 (ICAM-1) and B7.2. Internalization assays demonstrate that down regulation of each target can occur through increased endocytosis from the cell surface. However, mutation of a conserved tyrosine-based endocytosis motif in K5 resulted in a protein lacking the ability to direct an increased rate of MHC-I or ICAM-1 internalization but still able to down regulate B7.2 in a ubiquitin-dependent but endocytosis-independent manner. Further, mutation of two acidic clusters abolished K5-mediated MHC-I degradation while only slightly decreasing ICAM-1 or B7.2 protein destruction. This same mutant abolished detectable ubiquitylation of all targets. These data indicate that while K5 can act as an E3 ubiquitin ligase to directly mediate cell surface molecule destruction, regulation of its targets occurs through multiple pathways, including ubiquitin-independent mechanisms.

  17. The Kaposi's Sarcoma-Associated Herpesvirus K5 E3 Ubiquitin Ligase Modulates Targets by Multiple Molecular Mechanisms▿

    PubMed Central

    Means, Robert E.; Lang, Sabine M.; Jung, Jae U.

    2007-01-01

    Kaposi's sarcoma-associated herpesvirus encodes two highly related membrane-associated, RING-CH-containing (MARCH) family E3 ubiquitin ligases, K3 and K5, that can down regulate a variety of cell surface proteins through enhancement of their endocytosis and degradation. In this report we present data that while K5 modulation of major histocompatibility complex class I (MHC-I) closely mirrors the mechanisms used by K3, alternative molecular pathways are utilized by this E3 ligase in the down regulation of intercellular adhesion molecule 1 (ICAM-1) and B7.2. Internalization assays demonstrate that down regulation of each target can occur through increased endocytosis from the cell surface. However, mutation of a conserved tyrosine-based endocytosis motif in K5 resulted in a protein lacking the ability to direct an increased rate of MHC-I or ICAM-1 internalization but still able to down regulate B7.2 in a ubiquitin-dependent but endocytosis-independent manner. Further, mutation of two acidic clusters abolished K5-mediated MHC-I degradation while only slightly decreasing ICAM-1 or B7.2 protein destruction. This same mutant abolished detectable ubiquitylation of all targets. These data indicate that while K5 can act as an E3 ubiquitin ligase to directly mediate cell surface molecule destruction, regulation of its targets occurs through multiple pathways, including ubiquitin-independent mechanisms. PMID:17409151

  18. Passive immunization with anti-Tau antibodies in two transgenic models: reduction of Tau pathology and delay of disease progression.

    PubMed

    Chai, Xiyun; Wu, Su; Murray, Tracey K; Kinley, Robert; Cella, Claire V; Sims, Helen; Buckner, Nicola; Hanmer, Jenna; Davies, Peter; O'Neill, Michael J; Hutton, Michael L; Citron, Martin

    2011-09-30

    The microtubule-associated protein Tau plays a critical role in the pathogenesis of Alzheimer disease and several related disorders (tauopathies). In the disease Tau aggregates and becomes hyperphosphorylated forming paired helical and straight filaments, which can further condense into higher order neurofibrillary tangles in neurons. The development of this pathology is consistently associated with progressive neuronal loss and cognitive decline. The identification of tractable therapeutic targets in this pathway has been challenging, and consequently very few clinical studies addressing Tau pathology are underway. Recent active immunization studies have raised the possibility of modulating Tau pathology by activating the immune system. Here we report for the first time on passive immunotherapy for Tau in two well established transgenic models of Tau pathogenesis. We show that peripheral administration of two antibodies against pathological Tau forms significantly reduces biochemical Tau pathology in the JNPL3 mouse model. We further demonstrate that peripheral administration of the same antibodies in the more rapidly progressive P301S tauopathy model not only reduces Tau pathology quantitated by biochemical assays and immunohistochemistry, but also significantly delays the onset of motor function decline and weight loss. This is accompanied by a reduction in neurospheroids, providing direct evidence of reduced neurodegeneration. Thus, passive immunotherapy is effective at preventing the buildup of intracellular Tau pathology, neurospheroids, and associated symptoms, although the exact mechanism remains uncertain. Tau immunotherapy should therefore be considered as a therapeutic approach for the treatment of Alzheimer disease and other tauopathies.

  19. Charged-Higgs-boson effects in the B{yields}D{tau}{nu}{sub {tau}} differential decay distribution

    SciTech Connect

    Nierste, Ulrich; Trine, Stephanie; Westhoff, Susanne

    2008-07-01

    We show that the decay mode B{yields}D{tau}{nu}{sub {tau}} is competitive with and complementary to B{yields}{tau}{nu}{sub {tau}} in the search for charged-Higgs effects. Updating the relevant form factors, we find that the differential distribution in the decay chain B{yields}D{nu}{sub {tau}}{tau}{sup -}[{yields}{pi}{sup -}{nu}{sub {tau}}] excellently discriminates between standard model and charged-Higgs contributions. By measuring the D and {pi}{sup -} energies and the angle between the D and {pi}{sup -} three-momenta, one can determine the effective charged-Higgs coupling including a possible CP-violating phase.

  20. 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 ...

  1. 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

  2. Effects of the tropical ginger compound,1'-acetoxychavicol acetate, against tumor promotion in K5.Stat3C transgenic mice.

    PubMed

    Batra, Vinita; Syed, Zanobia; Gill, Jennifer N; Coburn, Malari A; Adegboyega, Patrick; DiGiovanni, John; Mathis, J Michael; Shi, Runhua; Clifford, John L; Kleiner-Hancock, Heather E

    2012-06-15

    The purpose of the current study was to determine whether a tropical ginger derived compound 1'-acetoxychavicol acetate (ACA), suppresses skin tumor promotion in K5.Stat3C mice. In a two-week study in which wild-type (WT) and K5.Stat3C mice were co-treated with either vehicle, ACA, galanga extract, or fluocinolone acetonide (FA) and tetradecanoyl phorbol acetate (TPA), only the galanga extract and FA suppressed TPA-induced skin hyperproliferation and wet weight. None of these agents were effective at suppressing p-Tyr705Stat3 expression. However, ACA and FA showed promising inhibitory effects against skin tumorigenesis in K5.Stat3C mice. ACA also suppressed phospho-p65 NF-κB activation, suggesting a potential mechanism for its action.

  3. 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.

  4. 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.

  5. Hsc70 rapidly engages tau after microtubule destabilization.

    PubMed

    Jinwal, Umesh K; O'Leary, John C; Borysov, Sergiy I; Jones, Jeffrey R; Li, Qingyou; Koren, John; Abisambra, Jose F; Vestal, Grant D; Lawson, Lisa Y; Johnson, Amelia G; Blair, Laura J; Jin, Ying; Miyata, Yoshinari; Gestwicki, Jason E; Dickey, Chad A

    2010-05-28

    The microtubule-associated protein Tau plays a crucial role in regulating the dynamic stability of microtubules during neuronal development and synaptic transmission. In a group of neurodegenerative diseases, such as Alzheimer disease and other tauopathies, conformational changes in Tau are associated with the initial stages of disease pathology. Folding of Tau into the MC1 conformation, where the amino acids at residues 7-9 interact with residues 312-342, is one of the earliest pathological alterations of Tau in Alzheimer disease. The mechanism of this conformational change in Tau and the subsequent effect on function and association to microtubules is largely unknown. Recent work by our group and others suggests that members of the Hsp70 family play a significant role in Tau regulation. Our new findings suggest that heat shock cognate (Hsc) 70 facilitates Tau-mediated microtubule polymerization. The association of Hsc70 with Tau was rapidly enhanced following treatment with microtubule-destabilizing agents. The fate of Tau released from the microtubule was found to be dependent on ATPase activity of Hsc70. Microtubule destabilization also rapidly increased the MC1 folded conformation of Tau. An in vitro assay suggests that Hsc70 facilitates formation of MC1 Tau. However, in a hyperphosphorylating environment, the formation of MC1 was abrogated, but Hsc70 binding to Tau was enhanced. Thus, under normal circumstances, MC1 formation may be a protective conformation facilitated by Hsc70. However, in a diseased environment, Hsc70 may preserve Tau in a more unstructured state, perhaps facilitating its pathogenicity.

  6. 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…

  7. Brackett-alpha line profiles of young stellar objects

    NASA Technical Reports Server (NTRS)

    Persson, S. E.; Geballe, T. R.; Mcgregor, P. J.; Edwards, S.; Lonsdale, C. J.

    1984-01-01

    Profiles of the Br-alpha line of H I at a velocity resolution of 45 km/s are presented for the compact imbedded infrared objects BN, S106/IRS 3, GLS 490, GL 961, GL 989, Mon. R2/IRS 2, and for the visible objects LkH-alpha 101, T Tau, and R Mon. A proportionality obtained between Br-alpha luminosity and bolometric luminosity is shown to extend over three orders of magnitude, supporting the idea that the physical conditions and gas motions in the circumstellar envelopes of stellar objects are closely related over a wide range of luminosities. The Br-alpha line strengths are compared to radio continuum flux densities in the context of stellar wind models. Momentum deposition rates deduced from Br-alpha or radio continuum fluxes are consistent with those available in the radiation fields, which appear capable of driving the ionized gas outflows in the vicinity of the core sources. The results of a comparison of the H-alpha and Br-alpha profiles for T Tau are discussed.

  8. Alzheimer-related decrease in CYFIP2 links amyloid production to tau hyperphosphorylation and memory loss

    PubMed Central

    Tiwari, Sachin Suresh; Mizuno, Keiko; Ghosh, Anshua; Aziz, Wajeeha; Troakes, Claire; Daoud, Jason; Golash, Vidushi; Noble, Wendy; Hortobágyi, Tibor

    2016-01-01

    Characteristic features of Alzheimer’s disease are memory loss, plaques resulting from abnormal processing of amyloid precursor protein (APP), and presence of neurofibrillary tangles and dystrophic neurites containing hyperphosphorylated tau. Currently, it is not known what links these abnormalities together. Cytoplasmic FMR1 interacting protein 2 (CYFIP2) has been suggested to regulate mRNA translation at synapses and this may include local synthesis of APP and alpha-calcium/calmodulin-dependent kinase II, a kinase that can phosphorylate tau. Further, CYFIP2 is part of the Wiskott-Aldrich syndrome protein-family verprolin-homologous protein complex, which has been implicated in actin polymerization at synapses, a process thought to be required for memory formation. Our previous studies on p25 dysregulation put forward the hypothesis that CYFIP2 expression is reduced in Alzheimer’s disease and that this contributes to memory impairment, abnormal APP processing and tau hyperphosphorylation. Here, we tested this hypothesis. First, in post-mortem tissue CYFIP2 expression was reduced by ∼50% in severe Alzheimer’s hippocampus and superior temporal gyrus when normalized to expression of a neuronal or synaptic marker protein. Interestingly, there was also a trend for decreased expression in mild Alzheimer’s disease hippocampus. Second, CYFIP2 expression was reduced in old but not in young Tg2576 mice, a model of familial Alzheimer’s disease. Finally, we tested the direct impact of reduced CYFIP2 expression in heterozygous null mutant mice. We found that in hippocampus this reduced expression causes an increase in APP and β-site amyloid precursor protein cleaving enzyme 1 (BACE1) protein, but not mRNA expression, and elevates production of amyloid-β42. Reduced CYFIP2 expression also increases alpha-calcium/calmodulin-dependent kinase II protein expression, and this is associated with hyperphosphorylation of tau at serine-214. The reduced expression also

  9. 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.

  10. 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.

  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. Detection of D-aspartate in tau proteins associated with Alzheimer paired helical filaments.

    PubMed

    Kenessey, A; Yen, S H; Liu, W K; Yang, X R; Dunlop, D S

    1995-03-27

    Paired helical filaments (PHF) characteristic of Alzheimer neurofibrillary lesions are known to contain a modified form of microtubule associated protein tau. These proteins, PHF-tau, differ from normal tau in the extent and the site of phosphorylation. To determine whether PHF-tau, tau proteins from normal adult brains (N-tau), tau proteins from Alzheimer brains not associated with PHF (A-tau), and tau proteins from fetal brains (F-tau) differ in racemization, these proteins were compared for their D-aspartate content. The results demonstrated that PHF-tau contain more D-aspartate than N-tau, A-tau and F-tau. The average percentage D-aspartate for these proteins, after a correction for background, are 4.9%, 2.8%, 1.6%, and 1% for PHF-tau, N-tau, A-tau and F-tau, respectively. It remains to be determined if the increase in D-aspartate is a consequence of PHF formation. It is also unknown if the change in D-aspartate content in PHF-tau is associated with phosphorylation, which alters the susceptibility of tau to proteolysis.

  13. Moving the School and Dancing Education: Case Study Research of K-5 Students' Experiences in a Dance Residency

    ERIC Educational Resources Information Center

    Leonard, Alison E.

    2012-01-01

    This dissertation chronicles the qualitative case study of a dance artist-in-residence at a diverse and inclusive K-5 school in an urban district, integrating science, social studies, physical education, music, and visual arts school curriculum and culminating in two public performances. This study focused on how students made meaning through this…

  14. The Relationship between Teacher Training, Intervention Strategies, and Students' Academic Achievement in the Classroom with K-5 ADHD Students

    ERIC Educational Resources Information Center

    Cooper, Nancy A.

    2014-01-01

    The primary intent of this study was to explore the effect between teachers' training, intervention strategies, and the academic achievement of K-5 ADHD students. The study design employed a mixed research design. The quantitative method focused on collecting data from certified regular and special-education teachers. Additionally, effects were…

  15. Examining the Internal Structure of the easyCBM Reading Measures, Grades K-5. Technical Report #1302

    ERIC Educational Resources Information Center

    Alonzo, Julie; Park, Bitnara Jasmine; Tindal, Gerald

    2013-01-01

    In this technical report, we describe a study examining the internal structures of the easyCBM reading measures, Grades K-5. Data were gathered from a convenience sample of 114 Kindergarten students, 43 first graders, 82 second graders, 100 third graders, 109 fourth graders, and 71 fifth graders attending schools in Oregon, Georgia, South…

  16. 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.

  17. Quantitative Characterization of Heparin Binding to Tau Protein

    PubMed Central

    Zhu, Hai-Li; Fernández, Cristina; Fan, Jun-Bao; Shewmaker, Frank; Chen, Jie; Minton, Allen P.; Liang, Yi

    2010-01-01

    Neurofibrillary tangles, principally composed of bundles of filaments formed by the microtubule-associated protein Tau, are a hallmark of a group of neurodegenerative diseases such as Alzheimer disease. Polyanionic cofactors such as heparin can induce Tau filament formation in vitro. Here we quantitatively characterize the interaction between recombinant human Tau fragment Tau244–372 and heparin (average molecular mass = 7 kDa) as well as heparin-induced fibril formation by using static light scattering, isothermal titration calorimetry, turbidity assays, and transmission electron microscopy. Our data clearly show that at physiological pH, heparin 7K, and human Tau244–372 form a tight 1:1 complex with an equilibrium association constant exceeding 106 m−1 under reducing conditions, triggering Tau fibrillization. In the absence of dithiothreitol, heparin shows a moderate binding affinity (105 m−1) to Tau244–372, similarly triggering Tau fibrillization. Further fibrillization kinetics analyses show that the lag time appears to be approximately invariant up to a molar ratio of 2:1 and then increases at larger ratios of heparin/Tau. The maximum slope representing the apparent rate constant for fibril growth increases sharply with substoichiometric ratios of heparin/Tau and then decreases to some extent with ratios of >1:1. The retarding effect of heparin in excess is attributed to the large increase in ionic strength of the medium arising from free heparin. Together, these results suggest that the formation of the 1:1 complex of Tau monomer and heparin plays an important role in the inducer-mediated Tau filament formation, providing clues to understanding the pathogenesis of neurodegenerative diseases. PMID:19959468

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

    PubMed

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

    2016-01-07

    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.

  19. 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.

  20. Lysosomal Dysfunction Promotes Cleavage and Neurotoxicity of Tau In Vivo

    PubMed Central

    Sharp, Katherine A.; Loewen, Carin A.; Mulkearns, Erin; Tyynelä, Jaana; Scherzer, Clemens R.; Feany, Mel B.

    2010-01-01

    Expansion of the lysosomal system, including cathepsin D upregulation, is an early and prominent finding in Alzheimer's disease brain. Cell culture studies, however, have provided differing perspectives on the lysosomal connection to Alzheimer's disease, including both protective and detrimental influences. We sought to clarify and molecularly define the connection in vivo in a genetically tractable model organism. Cathepsin D is upregulated with age in a Drosophila model of Alzheimer's disease and related tauopathies. Genetic analysis reveals that cathepsin D plays a neuroprotective role because genetic ablation of cathepsin D markedly potentiates tau-induced neurotoxicity. Further, generation of a C-terminally truncated form of tau found in Alzheimer's disease patients is significantly increased in the absence of cathepsin D. We show that truncated tau has markedly increased neurotoxicity, while solubility of truncated tau is decreased. Importantly, the toxicity of truncated tau is not affected by removal of cathepsin D, providing genetic evidence that modulation of neurotoxicity by cathepsin D is mediated through C-terminal cleavage of tau. We demonstrate that removing cathepsin D in adult postmitotic neurons leads to aberrant lysosomal expansion and caspase activation in vivo, suggesting a mechanism for C-terminal truncation of tau. We also demonstrate that both cathepsin D knockout mice and cathepsin D–deficient sheep show abnormal C-terminal truncation of tau and accompanying caspase activation. Thus, caspase cleavage of tau may be a molecular mechanism through which lysosomal dysfunction and neurodegeneration are causally linked in Alzheimer's disease. PMID:20664788

  1. 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

  2. Aluminum induces tau aggregation in vitro but not in vivo.

    PubMed

    Mizoroki, Tatsuya; Meshitsuka, Shunsuke; Maeda, Sumihiro; Murayama, Miyuki; Sahara, Naruhiko; Takashima, Akihiko

    2007-07-01

    Etiological studies suggest that aluminum (Al) intake might increase an individual's risk of developing Alzheimer's disease (AD). Biochemical analysis data on the effects of Al, however, are inconsistent. Hence, the pathological involvement of Al in AD remains unclear. If Al is involved in AD, then it is reasonable to hypothesize that Al might be involved in the formation of either amyloid plaques or neurofibrillary tangles (NFTs). Here, we investigated whether Al might be involved in NFT formation by using an in vitro tau aggregation paradigm, a tau-overexpressing neuronal cell line (N2a), and a tau-overexpressing mouse model. Although Al induced tau aggregation in a heparin-induced tau assembly assay, these aggregates were neither thioflavin T positive nor did they resemble tau fibrils seen in human AD brains. With cell lysates from stable cell lines overexpressing tau, the accumulation of SDS-insoluble tau increased when the lysates were treated with at least 100 muM Al-maltolate. Yet Al-maltolate caused illness or death in transgenic mice overexpressing human tau and in non-transgenic littermates well before the Al concentration in the brain reached 100 muM. These results indicate that Al has no direct link to AD pathology.

  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. 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

  5. Tau protein in normal and Alzheimer's disease brain: an update.

    PubMed

    Johnson, G V; Hartigan, J A

    1999-11-01

    Tau is a microtubule-associated protein that, in a hyperphosphorylated form, comprises the main component of the paired helical filaments and neurofibrillary tangles found in Alzheimer's Disease (AD) brain. It is therefore important to understand the normal functioning and processing of tau protein, and the abnormal posttranslational processing of tau in AD pathology. In 1996, Johnson and Jenkins reviewed the literature on the biochemistry, function, and phosphorylation of tau in normal and AD brain. Since that time, numerous publications have come out further elucidating the properties of tau. The present review updates the topics originally covered in the 1996 review, as well as presents a number of new topics. For example, mutations in the tau gene have been found in several non-AD, autosomal dominant neurodegenerative disorders that exhibit extensive neurofibrillary pathology. In addition, there is increasing evidence that tau may be involved in signal transduction, organelle transport, and cell growth, independent of its microtubule-binding functions. Taken together, the research reviewed here demonstrates that tau is a very complex protein with various functions that are intricately regulated. It is clear that more research is required to completely understand the functions and regulation of tau in normal and AD brain.

  6. Tau approximation techniques for identification of coefficients in parabolic PDE

    NASA Technical Reports Server (NTRS)

    Banks, H. T.; Wade, J. G.

    1989-01-01

    A variant of the Tau method, called the weak Tau method, is developed on the basis of the weak form of the PDE for use in least-squares parameter estimation; also presented is a suitable abstract convergence framework. The emphasis is on the theoretical framework that allows treatment of the weak Tau method when it is applied to a wide class of inverse problems, including those for diffusion-advection equations, the Fokker-Planck model for population dynamics, and damped beam equations. Extensive numerical testing of the weak Tau method has demonstrated that it compares quite favorably with existing methods.

  7. The Importance of Tau Phosphorylation for Neurodegenerative Diseases

    PubMed Central

    Noble, Wendy; Hanger, Diane P.; Miller, Christopher C. J.; Lovestone, Simon

    2013-01-01

    Fibrillar deposits of highly phosphorylated tau are a key pathological feature of several neurodegenerative tauopathies including Alzheimer’s disease (AD) and some frontotemporal dementias. Increasing evidence suggests that the presence of these end-stage neurofibrillary lesions do not cause neuronal loss, but rather that alterations to soluble tau proteins induce neurodegeneration. In particular, aberrant tau phosphorylation is acknowledged to be a key disease process, influencing tau structure, distribution, and function in neurons. Although typically described as a cytosolic protein that associates with microtubules and regulates axonal transport, several additional functions of tau have recently been demonstrated, including roles in DNA stabilization, and synaptic function. Most recently, studies examining the trans-synaptic spread of tau pathology in disease models have suggested a potential role for extracellular tau in cell signaling pathways intrinsic to neurodegeneration. Here we review the evidence showing that tau phosphorylation plays a key role in neurodegenerative tauopathies. We also comment on the tractability of altering phosphorylation-dependent tau functions for therapeutic intervention in AD and related disorders. PMID:23847585

  8. Hyperphosphorylated Tau is Elevated in Alzheimer's Disease with Psychosis

    PubMed Central

    Murray, Patrick S.; Kirkwood, Caitlin M.; Gray, Megan C.; Fish, Kenneth N.; Ikonomovic, Milos D.; Hamilton, Ronald L.; Kofler, Julia K.; Klunk, William E.; Lopez, Oscar L.; Sweet, Robert A.

    2014-01-01

    Psychosis occurs in 40–60% of Alzheimer's disease (AD) subjects, is heritable, and indicates amore rapidly progressive disease phenotype. Neuroimaging and postmortem evidence support an exaggerated prefrontal cortical synaptic deficit in AD with psychosis. Microtubule-associated protein tau is a key mediator of amyloid-β-induced synaptotoxicity in AD, and differential mechanisms of progressive intraneuronal phospho-tau accumulation and interneuronal spread of tau aggregates have recently been described. We hypothesized that psychosis in AD would be associated with greater intraneuronal concentration of phospho-tau and greater spread of tau aggregates in prefrontal cortex. We therefore evaluated prefrontal cortex phospho-tau in a cohort of 45 AD cases with and without psychosis. Intraneuronal phospho-tau concentration was higher in subjects with psychosis, while a measure of phospho-tau spread, volume fraction, was not. Across groups both measures were associated with lower scores on the Mini-Mental State Examination and Digit Span Backwards test. These novel findings indicate that tau phosphorylation may be accelerated in AD with psychosis, indicating a more dynamic, exaggerated pathology in AD with psychosis. PMID:24270207

  9. Salivary tau species are potential biomarkers of Alzheimer's disease.

    PubMed

    Shi, Min; Sui, Yu-Ting; Peskind, Elaine R; Li, Ge; Hwang, HyeJin; Devic, Ivana; Ginghina, Carmen; Edgar, John Scott; Pan, Catherine; Goodlett, David R; Furay, Amy R; Gonzalez-Cuyar, Luis F; Zhang, Jing

    2011-01-01

    Phosphorylation of tau protein is a critical event in the pathogenesis of Alzheimer's disease (AD). Increased phosphorylated tau and total tau levels, combined with reduced concentrations of amyloid-β 1-42 (Aβ42) in cerebrospinal fluid (CSF), but not in plasma or serum, have been generally accepted as sensitive AD diagnostic markers. However, obtaining CSF is a relatively invasive procedure that requires participation of specially trained medical professionals, i.e., CSF is not an ideal sample source for screening or early diagnosis of AD, which is essential to current and future neuroprotective treatments for the disease. Here, we identified tau, but not Aβ species, with mass spectrometry in human saliva, a body fluid that is much more accessible compared to CSF or even blood. Quantitative assessment of salivary levels of total tau, phosphorylated tau, and Aβ42 using highly sensitive Luminex assays revealed that, while Aβ42 was not detectable, the phosphorylated tau/tau ratio significantly increased in patients with AD compared to healthy controls. These results suggest that salivary tau species could be ideal biomarkers for AD diagnosis, especially at early stages of the disease or even screening asymptomatic subjects, allowing for a much larger therapeutic window for AD patients. PMID:21841250

  10. 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.

  11. Measurements of Charged Current Lepton Universality and |V{sub us}| Using Tau Lepton Decays to e{sup -{nu}}{sub e{nu}{tau}}, {mu}{sup -{nu}}{sub {mu}{nu}{tau}}, {pi}{sup -{nu}}{sub {tau},} and K{sup -{nu}}{sub {tau}}

    SciTech Connect

    Aubert, B.; Karyotakis, Y.; Lees, J. P.; Poireau, V.; Prencipe, E.; Prudent, X.; Tisserand, V.; 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.

    2010-07-30

    Using 467 fb{sup -1} of e{sup +}e{sup -} annihilation data collected with the BABAR detector, we measure (B({tau}{sup -{yields}}{mu}-{nu}{sub {mu}{nu}{tau}}))/B({tau}{sup -{yields}}e{sup -{nu}}{sub e{nu}{tau}})=(0.9796{+-}0.0016{+-}0.0036), (B({tau}{sup -{yields}}{pi}-{nu}{sub {tau}})/B({tau}{sup -{yields}}e{sup -{nu}}{sub e{nu}{tau}}))=(0.5945{+-}0.0014{+-}0.0061), and (B({tau}{sup -{yields}}K{sup -{nu}}{sub {tau}})/B({tau}{sup -{yields}}e{sup -{nu}}{sub e{nu}{tau}}))=(0.03882{+-}0.00032{+-}0.00057), where the uncertainties are statistical and systematic, respectively. From these precision {tau} measurements, we test the standard model assumption of {mu}-e and {tau}-{mu} charge current lepton universality and provide determinations of |V{sub us}| experimentally independent of the decay of a kaon.

  12. Observation of B{sup 0}{yields}D*{sup -}{tau}{sup +}{nu}{sub {tau}} Decay at Belle

    SciTech Connect

    Matyja, A.; Rozanska, M.; Bozek, A.; Lesiak, T.; Natkaniec, Z.; Palka, H.; Adachi, I.; Brodzicka, J.; Haba, J.; Hazumi, M.; Itoh, R.; Iwasaki, Y.; Katayama, N.; Kichimi, H.; Krokovny, P.; Nakamura, I.; Nakao, M.; Nishida, S.; Nozaki, T.; Ozaki, H.

    2007-11-09

    We report an observation of the decay B{sup 0}{yields}D*{sup -}{tau}{sup +}{nu}{sub {tau}} in a data sample containing 535x10{sup 6} BB pairs collected with the Belle detector at the KEKB asymmetric-energy e{sup +}e{sup -} collider. We find a signal with a significance of 5.2{sigma} and measure the branching fraction B(B{sup 0}{yields}D*{sup -}{tau}{sup +}{nu}{sub {tau}})=(2.02{sub -0.37}{sup +0.40}(stat){+-}0.37(syst)) = %. This is the first observation of an exclusive B decay with a b{yields}c{tau}{nu}{sub {tau}} transition.

  13. 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.

  14. 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

  15. The creep behavior of gamma alloy Ti-46.5Al-3Nb-2Cr-0.2W (alloy K5) in two microstructural conditions

    SciTech Connect

    Schwenker, S.W.; Kim, Y.W.

    1995-12-31

    The creep behavior of a wrought gamma alloy Ti-46.5Al-3Nb-2Cr-0.2W (Alloy K5) has been investigated in both a fine-grained duplex ({approximately}10 {micro}m grain size) and a refined fully-lamellar (RFL) microstructural condition (average lamellar grain size of {approximately} 300 {micro}m). Creep tests were conducted in laboratory air under constant tensile load at temperatures between 676 and 870 C and stresses between 69 and 242 MPa. The results show that the RFL condition exhibits creep resistance significantly improved over the duplex microstructure. At 800 C and 138 MPa the RFL material exhibited a secondary or minimum creep rate of 3.8 {times} 10{sup {minus}5} h{sup {minus}1} which is nearly two orders of magnitude slower than for the fine duplex. Activation energies and stress exponents for power law creep were measured and found to be similar for the two microstructures over the range of conditions investigated. Microstructural studies conducted on crept RFL specimens showed evidence of bulk deformation within the lamellar grains which lead to break up or spheroidization of the {alpha}{sub 2} laths at high creep strains. Creep failure occurred by intergranular cracking and cavity formation along grain boundaries in the material.

  16. Mobility and subcellular localization of endogenous, gene-edited Tau differs from that of over-expressed human wild-type and P301L mutant Tau

    PubMed Central

    Di Xia; Gutmann, Julia M.; Götz, Jürgen

    2016-01-01

    Alzheimer’s disease (AD) and a subset of frontotemporal dementia termed FTLD-Tau are characterized by a massive, yet incompletely characterized and understood redistribution of Tau. To establish a framework for understanding this pathology, we used the genome-editing tool TALEN and generated Tau-mEOS2 knock-in mice to determine the mobility and subcellular localization of endogenous Tau in hippocampal cultures. We analysed Tau in axons, dendrites and spines at three stages of maturation using live-cell imaging, photo-conversion and FRAP assays. Tau-mEOS2 cultures were compared with those over-expressing EGFP-tagged forms of human wild-type (hWT-Tau) and P301L mutant Tau (hP301L-Tau), modelling Tau accumulation in AD and FTLD-Tau, respectively. In developing neurons, Tau-mEOS2 followed a proximo-distal gradient in axons and a subcellular distribution similar to that of endogenous Tau in neurons obtained from wild-type mice, which were abolished, when either hWT-Tau or hP301L-Tau was over-expressed. For the three conditions, FRAP analysis revealed a similar mobility in dendrites compared with axons; however, Tau-mEOS2 was less mobile than hWT-Tau and hP301L-Tau and the mobile fraction was smaller, possibly reflecting less efficient microtubule binding of Tau when over-expressed. Together, our study presents Tau-mEOS2 mice as a novel tool for the study of Tau in a physiological and a pathological context. PMID:27378256

  17. 18F-AV-1451 tau PET imaging correlates strongly with tau neuropathology in MAPT mutation carriers

    PubMed Central

    Puschmann, Andreas; Schöll, Michael; Ohlsson, Tomas; van Swieten, John; Honer, Michael; Englund, Elisabet

    2016-01-01

    Tau positron emission tomography ligands provide the novel possibility to image tau pathology in vivo. However, little is known about how in vivo brain uptake of tau positron emission tomography ligands relates to tau aggregates observed post-mortem. We performed tau positron emission tomography imaging with 18F-AV-1451 in three patients harbouring a p.R406W mutation in the MAPT gene, encoding tau. This mutation results in 3- and 4-repeat tau aggregates similar to those in Alzheimer’s disease, and many of the mutation carriers initially suffer from memory impairment and temporal lobe atrophy. Two patients with short disease duration and isolated memory impairment exhibited 18F-AV-1451 uptake mainly in the hippocampus and adjacent temporal lobe regions, correlating with glucose hypometabolism in corresponding regions. One patient died after 26 years of disease duration with dementia and behavioural deficits. Pre-mortem, there was 18F-AV-1451 uptake in the temporal and frontal lobes, as well as in the basal ganglia, which strongly correlated with the regional extent and amount of tau pathology in post-mortem brain sections. Amyloid-β (18F-flutemetamol) positron emission tomography scans were negative in all cases, as were stainings of brain sections for amyloid. This provides strong evidence that 18F-AV-1451 positron emission tomography can be used to accurately quantify in vivo the regional distribution of hyperphosphorylated tau protein. PMID:27357347

  18. 18F-AV-1451 tau PET imaging correlates strongly with tau neuropathology in MAPT mutation carriers.

    PubMed

    Smith, Ruben; Puschmann, Andreas; Schöll, Michael; Ohlsson, Tomas; van Swieten, John; Honer, Michael; Englund, Elisabet; Hansson, Oskar

    2016-09-01

    Tau positron emission tomography ligands provide the novel possibility to image tau pathology in vivo However, little is known about how in vivo brain uptake of tau positron emission tomography ligands relates to tau aggregates observed post-mortem. We performed tau positron emission tomography imaging with (18)F-AV-1451 in three patients harbouring a p.R406W mutation in the MAPT gene, encoding tau. This mutation results in 3- and 4-repeat tau aggregates similar to those in Alzheimer's disease, and many of the mutation carriers initially suffer from memory impairment and temporal lobe atrophy. Two patients with short disease duration and isolated memory impairment exhibited (18)F-AV-1451 uptake mainly in the hippocampus and adjacent temporal lobe regions, correlating with glucose hypometabolism in corresponding regions. One patient died after 26 years of disease duration with dementia and behavioural deficits. Pre-mortem, there was (18)F-AV-1451 uptake in the temporal and frontal lobes, as well as in the basal ganglia, which strongly correlated with the regional extent and amount of tau pathology in post-mortem brain sections. Amyloid-β ((18)F-flutemetamol) positron emission tomography scans were negative in all cases, as were stainings of brain sections for amyloid. This provides strong evidence that (18)F-AV-1451 positron emission tomography can be used to accurately quantify in vivo the regional distribution of hyperphosphorylated tau protein.

  19. Searches for Lepton flavor violation in the decays tau{+/-}-->e{+/-}gamma and tau{+/-}-->mu{+/-}gamma.

    PubMed

    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; Hooberman, B; 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; 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; 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; Morii, M; Adametz, A; Marks, J; Schenk, S; Uwer, U; Bernlochner, F U; Lacker, H M; Lueck, T; Volk, A; 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; D'Orazio, A; Davier, M; Derkach, D; Firmino da Costa, J; Grosdidier, G; Le Diberder, F; Lepeltier, V; Lutz, A M; Malaescu, B; 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; Nguyen, X; 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; 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; Li Gioi, L; 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; Bard, D J; 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; Franco Sevilla, M; Fulsom, B G; 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; Lindsay, C D; Locke, C B; 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

    2010-01-15

    Searches for lepton-flavor-violating decays of a tau lepton to a lighter mass lepton and a photon have been performed with the entire data set of (963+/-7)x10{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 we set upper limits on the branching fractions of B(tau{+/-}-->e{+/-}gamma)<3.3x10{-8} and B(tau{+/-}-->mu{+/-}gamma)<4.4x10{-8} at 90% confidence level. PMID:20366586

  20. 18F-AV-1451 tau PET imaging correlates strongly with tau neuropathology in MAPT mutation carriers.

    PubMed

    Smith, Ruben; Puschmann, Andreas; Schöll, Michael; Ohlsson, Tomas; van Swieten, John; Honer, Michael; Englund, Elisabet; Hansson, Oskar

    2016-09-01

    Tau positron emission tomography ligands provide the novel possibility to image tau pathology in vivo However, little is known about how in vivo brain uptake of tau positron emission tomography ligands relates to tau aggregates observed post-mortem. We performed tau positron emission tomography imaging with (18)F-AV-1451 in three patients harbouring a p.R406W mutation in the MAPT gene, encoding tau. This mutation results in 3- and 4-repeat tau aggregates similar to those in Alzheimer's disease, and many of the mutation carriers initially suffer from memory impairment and temporal lobe atrophy. Two patients with short disease duration and isolated memory impairment exhibited (18)F-AV-1451 uptake mainly in the hippocampus and adjacent temporal lobe regions, correlating with glucose hypometabolism in corresponding regions. One patient died after 26 years of disease duration with dementia and behavioural deficits. Pre-mortem, there was (18)F-AV-1451 uptake in the temporal and frontal lobes, as well as in the basal ganglia, which strongly correlated with the regional extent and amount of tau pathology in post-mortem brain sections. Amyloid-β ((18)F-flutemetamol) positron emission tomography scans were negative in all cases, as were stainings of brain sections for amyloid. This provides strong evidence that (18)F-AV-1451 positron emission tomography can be used to accurately quantify in vivo the regional distribution of hyperphosphorylated tau protein. PMID:27357347

  1. Discoveries of tau, abnormally hyperphosphorylated tau and others of neurofibrillary degeneration: a personal historical perspective.

    PubMed

    Iqbal, Khalid; Grundke-Iqbal, Inge

    2006-01-01

    Alzheimer disease was described by Alois Alzheimer in 1907, but it was not until approximately 60-70 years later that any new significant developments were reported on the pathology of this disease. The discoveries that laid down the foundation for the exciting research that has been carried out during the last approximately 20 years and that have significantly enhanced our understanding of the disease are the ultrastructure of neurofibrillary tangles and neuritic (senile) plaques, the clinical-pathological correlation of these lesions to the presence of dementia, and the bulk isolation and protein composition of paired helical filaments and plaque amyloid. We discovered tau as the major protein subunit of paired helical filaments/neurofibrillary tangles, the abnormal hyperphosphorylation of this protein in this lesion and in Alzheimer brain cytosol and the gain of toxic function by the cytosolic abnormally hyperphosphorylated tau in Alzheimer brain. Here we present a personal historical account of the work in our laboratories that led, in 1986, to the discoveries of tau and its abnormal hyperphosphorylation in paired helical filaments and Alzheimer brain cytosol. This article also describes several major findings which subsequently resulted from the abnormal hyperphosphorylation of tau and in a large part account for the current understanding of the role of this lesion in Alzheimer disease and other tauopathies.

  2. Constraining new interactions with leptonic {tau} decays

    SciTech Connect

    Pich, A.; Silva, J.P.

    1995-10-01

    The recent measurements of the Michel parameters in {tau} decays enable, for the first time, a thorough analysis of the leptonic sector. In general, in models beyond the standard model, these parameters will be altered through changes in the {ital W} and {ital Z} couplings, and/or through interactions mediated by new gauge bosons. We perform a complete, model-independent analysis of the constraints imposed by the present data on such boson-mediated interactions, and point out the existence of useful relations among the couplings.

  3. Alpha-1 Antitrypsin Deficiency

    MedlinePlus

    ... Liver Disease Information > Alpha-1 Antitrypsin Deficiency Alpha-1 Antitrypsin Deficiency Explore this section to learn more about alpha-1 antitrypsin deficiency, including a description of the disorder ...

  4. An immunochemical study on tau glycation in paired helical filaments.

    PubMed

    Ko, L W; Ko, E C; Nacharaju, P; Liu, W K; Chang, E; Kenessey, A; Yen, S H

    1999-06-01

    Glycation is a non-enzymatic posttranslational modification that involves a covalent linkage between a sugar and an amino group of protein molecule forming ketoamine. Subsequent oxidation, fragmentation and/or crosslinking of ketoamine leads to the production of advanced glycation endproducts (AGEs). Formation of AGEs causes detrimental effects on the structure and function of affected proteins. Accumulation of AGEs has been implicated in normal aging and in the pathogenesis of diabetes-associated complications and Alzheimer's disease (AD). Of all AGEs, Nepsilon-(carboxymethyl)lysine (CML) is a major glycoxidation product known to be stable and accumulate progressively in vivo. In order to determine if tau is glycated in AD, we raised a rabbit antibody to CML that demonstrated its usefulness in detecting glycation of different proteins in vitro, including BSA, ribonuclease, lysozyme and recombinant tau. Immunochemical analyses indicated that ribose and glucose-6-phosphate are more effective than glucose in generating CML formation in these proteins. We used this antibody to probe for glycation in the following human tau preparations: tau of normal brains and preparations of soluble PHF-tau as well as insoluble PHF from AD brains. All three principal tau components resolved from PHF-tau on Western blots showed CML immunoreactivity indicating that tau is glycated in PHF-tau; and insoluble PHF exhibited prominent CML immunoreactivity on top of the stacking gel. Moreover, immunoelectron microscopic analyses indicate that the anti-CML antibody labels predominantly PHF in aggregates. Taken together, these results suggest that tau becomes glycated in PHF-tau and glycation may play a role in stabilizing PHF aggregation leading to tangle formation in AD.

  5. K5/K14-positive cells contribute to salivary gland-like breast tumors with myoepithelial differentiation.

    PubMed

    Boecker, Werner; Stenman, Goeran; Loening, Thomas; Andersson, Mattias K; Bankfalvi, Agnes; von Holstein, Sarah; Heegaard, Steffen; Lange, Alina; Berg, Tobias; Samoilova, Vera; Tiemann, Katharina; Buchwalow, Igor

    2013-08-01

    Salivary gland-like tumors of the breast show a great variety of architectural patterns and cellular differentiations such as glandular, myoepithelial, squamous, and even mesenchymal phenotypes. However, currently little is known about the evolution and cellular differentiation of these tumors. For that reason, we performed an in situ triple immunofluorescence lineage/differentiation tracing (isTILT) and qRT-PCR study of basal (K5/K14), glandular (K7/K8/18), and epidermal-specific squamous (K10) keratins, p63, and smooth muscle actin (SMA; myoepithelial marker) with the aim to construct and trace different cell lineages and define their cellular hierarchy in tumors with myoepithelial differentiation. isTILT analysis of a series of 28 breast, salivary, and lacrimal gland tumors, including pleomorphic adenomas (n=8), epithelial-myoepithelial tumors (n=9), and adenoid cystic carcinomas (n=11) revealed that all tumor types contained K5/K14-positive progenitor cells in varying frequencies from a few percent up to 15%. These K5/K14-positive tumor cells were found to differentiate to glandular- (K8/18-positive) and myoepithelial-lineage (SMA-positive)-specific cells and were also shown to generate various heterologeous cell differentiations such as squamous and mesenchymal progenies. p63 was co-expressed with K5/K14 in basal-like progenitor cells, myoepithelial, and squamous cells but not in glandular cells. Our results show that the corresponding counterpart tumors of breast and salivary/lacrimal glands have identical cellular compositions. Taken together, our isTILT and RNA-expression data indicate that look-alike tumors of the breast represent a special subgroup of basal-type tumors with benign or usually low malignant potential.

  6. Somatic mutations in MAP3K5 attenuate its pro-apoptotic function in melanoma through increased binding to Thioredoxin

    PubMed Central

    Prickett, Todd D.; Zerlanko, Brad; Gartner, Jared J.; Parker, Stephen C. J.; Dutton-Regester, Ken; Lin, Jimmy C.; Teer, Jamie K.; Wei, Xiaomu; Jiang, Jiji; Chen, Guo; Davies, Michael A.; Gershenwald, Jeffrey E.; Robinson, William; Robinson, Steven; Hayward, Nicholas K.; Rosenberg, Steven, A.; Margulies, Elliott H.; Samuels, Yardena

    2013-01-01

    Patients with advanced metastatic melanoma have poor prognosis and the genetics underlying its pathogenesis are poorly understood. High throughput sequencing has allowed comprehensive discovery of somatic mutations in cancer samples. Here, upon analysis of our whole-genome and whole-exome sequencing data of 29 melanoma samples we identified several genes that harbor recurrent non-synonymous mutations. These included MAP3K5, which in a prevalence screen of 288 melanomas was found to harbor a R256C substitution in 5 cases. All MAP3K5 mutated samples were wild-type for BRAF, suggesting a mutual exclusivity for these mutations. Functional analysis of the MAP3K5 R256C mutation revealed attenuation of MKK4 activation through increased binding of the inhibitory protein thioredoxin (TXN/TRX-1/Trx); resulting in increased proliferation and anchorage-independent growth of melanoma cells. This mutation represents a potential target for the design of new therapies to treat melanoma. PMID:24008424

  7. Final report of COOMET.T-K5: realizations of the ITS-90 at 1084.62 °C

    NASA Astrophysics Data System (ADS)

    Sergiyenko, R. P.; Matveyev, M. S.

    2015-01-01

    At the meeting of the Technical Committee 1.10 of COOMET in 2007 it was decided to undertake a regional comparison between the VNIIM (Russian Federation) and the NSC IM (Ukraine) for realization of the ITS-90 at the freezing point of copper in the field of non-contact thermometry. The VNIIM participated in the key comparisons CCT-K5. As a consequence, the VNIIM therefore acts as the linking institute for this comparison, registered in the KCDB as COOMET.T-K5, to disseminate metrological equivalence to the NSC IM standards (Ukraine). The protocol of the comparison covers two separate comparisons: a comparison of fixed-point cells (Stage 1), and a comparison of lamp calibrations (Stage 2) at 1084.62 °C. The results of the Stage 2 comparison are used in this report for linkage with the CCT-K5. 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 CCT, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  8. Dynamic Competing Histone H4 K5K8 Acetylation and Butyrylation Are Hallmarks of Highly Active Gene Promoters

    PubMed Central

    Goudarzi, Afsaneh; Zhang, Di; Huang, He; Barral, Sophie; Kwon, Oh Kwang; Qi, Shankang; Tang, Zhanyun; Buchou, Thierry; Vitte, Anne-Laure; He, Tieming; Cheng, Zhongyi; Montellier, Emilie; Gaucher, Jonathan; Curtet, Sandrine; Debernardi, Alexandra; Charbonnier, Guillaume; Puthier, Denis; Petosa, Carlo; Panne, Daniel; Rousseaux, Sophie; Roeder, Robert G.; Zhao, Yingming; Khochbin, Saadi

    2016-01-01

    Summary Recently discovered histone lysine acylation marks increase the functional diversity of nucleosomes well beyond acetylation. Here, we focus on histone butyrylation in the context of sperm cell differentiation. Specifically, we investigate the butyrylation of histone H4 lysine 5 and 8 at gene promoters where acetylation guides the binding of Brdt, a bromodomain-containing protein, thereby mediating stage-specific gene expression programs and post-meiotic chromatin reorganization. Genome-wide mapping data show that highly active Brdt-bound gene promoters systematically harbor competing histone acetylation and butyrylation marks at H4 K5 and H4 K8. Despite acting as a direct stimulator of transcription, histone butyrylation competes with acetylation, especially at H4 K5, to prevent Brdt binding. Additionally, H4 K5K8 butyrylation also marks retarded histone removal during late spermatogenesis. Hence, alternating H4 acetylation and butyrylation, while sustaining direct gene activation and dynamic bromodomain binding, could impact the final male epigenome features. PMID:27105113

  9. Dynamic Competing Histone H4 K5K8 Acetylation and Butyrylation Are Hallmarks of Highly Active Gene Promoters.

    PubMed

    Goudarzi, Afsaneh; Zhang, Di; Huang, He; Barral, Sophie; Kwon, Oh Kwang; Qi, Shankang; Tang, Zhanyun; Buchou, Thierry; Vitte, Anne-Laure; He, Tieming; Cheng, Zhongyi; Montellier, Emilie; Gaucher, Jonathan; Curtet, Sandrine; Debernardi, Alexandra; Charbonnier, Guillaume; Puthier, Denis; Petosa, Carlo; Panne, Daniel; Rousseaux, Sophie; Roeder, Robert G; Zhao, Yingming; Khochbin, Saadi

    2016-04-21

    Recently discovered histone lysine acylation marks increase the functional diversity of nucleosomes well beyond acetylation. Here, we focus on histone butyrylation in the context of sperm cell differentiation. Specifically, we investigate the butyrylation of histone H4 lysine 5 and 8 at gene promoters where acetylation guides the binding of Brdt, a bromodomain-containing protein, thereby mediating stage-specific gene expression programs and post-meiotic chromatin reorganization. Genome-wide mapping data show that highly active Brdt-bound gene promoters systematically harbor competing histone acetylation and butyrylation marks at H4 K5 and H4 K8. Despite acting as a direct stimulator of transcription, histone butyrylation competes with acetylation, especially at H4 K5, to prevent Brdt binding. Additionally, H4 K5K8 butyrylation also marks retarded histone removal during late spermatogenesis. Hence, alternating H4 acetylation and butyrylation, while sustaining direct gene activation and dynamic bromodomain binding, could impact the final male epigenome features. PMID:27105113

  10. Studies of tau- to h- h- h+ nu and tau- to K- pi0 nu Decays at BaBar

    SciTech Connect

    Nugent, I.M.; /Victoria U.

    2007-10-24

    We present preliminary inclusive branching fraction measurements of {tau}{sup -} {yields} h{sup -}h{sup -}h{sup +}{nu} (h = {pi} or K) and {tau}{sup -} K{sup -}{pi}{sup 0}{nu} decay modes using a sample of {tau}-pair events collected by the BABAR detector at the SLAC PEP-II asymmetric e{sup +}e{sup -} storage ring. The branching fractions of {tau}{sup -} {yields} {pi}{sup -}{pi}{sup -}{pi}{sup +}, {tau}{sup -} {yields} K{sup -}{pi}{sup -}{pi}{sup +}{nu}, and {tau}{sup -} {yields} K{sup -}{pi}{sup -}K{sup +}{nu} are measured with higher precision than previously published results and the inclusive branching fraction {tau}{sup -} {yields} K{sup -}K{sup -}K{sup +}{nu} is measured for the first time. In addition, the first measurement of the branching fraction {tau}{sup -} {yields} {pi}{sup -}{phi}{nu} and the measurement of the branching fraction {tau}{sup -} {yields} K{sup -}{phi}{nu} are determined by means of a binned maximum likelihood fit to the K{sup +}K{sup -} invariant mass distribution. These branching fractions are extracted by means of a migration matrix that accounts for the cross contamination between the {tau}{sup -} {yields} h{sup -}h{sup -}h{sup +}{nu} modes. The preliminary {tau}{sup -} {yields} K{sup -}{pi}{sup 0}{nu} branching fraction and invariant mass distributions are also presented in this paper.

  11. Microtubule-associated protein tau (tau) is a major antigenic component of paired helical filaments in Alzheimer disease.

    PubMed Central

    Kosik, K S; Joachim, C L; Selkoe, D J

    1986-01-01

    The detailed protein composition of the paired helical filaments (PHF) that accumulate in human neurons in aging and Alzheimer disease is unknown. However, the identity of certain components has been surmised by using immunocytochemical techniques. Whereas PHF share epitopes with neurofilament proteins and microtubule-associated protein (MAP) 2, we report evidence that the MAP tau (tau) appears to be their major antigenic component. Immunization of rabbits with NaDodSO4-extracted, partially purified PHF (free of normal cytoskeletal elements, including tau) consistently produces antibodies to tau but not, for example, to neurofilaments. Such PHF antibodies label all of the heterogeneous fetal and mature forms of tau from rat and human brain. Absorption of PHF antisera with heat-stable MAPs (rich in tau) results in almost complete loss of staining of neurofibrillary tangles (NFT) in human brain sections. An affinity-purified antibody to tau specifically labels NFT and the neurites of senile plaques in human brain sections as well as NaDodSO4-extracted NFT. tau-Immunoreactive NFT frequently extend into the apical dendrites of pyramidal neurons, suggesting an aberrant intracellular locus for this axonal protein. tau and PHF antibodies label tau proteins identically on electrophoretic transfer blots and stain the gel-excluded protein representing NaDodSO4-insoluble PHF in homogenates of human brain. The progressive accumulation of altered tau protein in neurons in Alzheimer disease may result in instability of microtubules, consequent loss of effective transport of molecules and organelles, and, ultimately, neuronal death. Images PMID:2424016

  12. Tau and neurodegenerative disease: the story so far.

    PubMed

    Iqbal, Khalid; Liu, Fei; Gong, Cheng-Xin

    2016-01-01

    In 1975, tau protein was isolated as a microtubule-associated factor from the porcine brain. In the previous year, a paired helical filament (PHF) protein had been identified in neurofibrillary tangles in the brains of individuals with Alzheimer disease (AD), but it was not until 1986 that the PHF protein and tau were discovered to be one and the same. In the AD brain, tau was found to be abnormally hyperphosphorylated, and it inhibited rather than promoted in vitro microtubule assembly. Almost 80 disease-causing exonic missense and intronic silent mutations in the tau gene have been found in familial cases of frontotemporal dementia but, to date, no such mutation has been found in AD. The first phase I clinical trial of an active tau immunization vaccine in patients with AD was recently completed. Assays for tau levels in cerebrospinal fluid and plasma are now available, and tau radiotracers for PET are under development. In this article, we provide an overview of the pivotal discoveries in the tau research field over the past 40 years. We also review the current status of the field, including disease mechanisms and therapeutic approaches. PMID:26635213

  13. Importance of precision measurements in the tau sector

    SciTech Connect

    Pich, A.

    1996-01-01

    {tau} decays provide a powerful tool to test the structure of the weak currents and the universality of their couplings to the {ital W} boson. The constraints implied by present data and the possible improvements at the {tau}cF are analyzed. {copyright} {ital 1996 American Institute of Physics.}

  14. The many faces of interferon tau.

    PubMed

    Bazer, Fuller W; Ying, Wei; Wang, Xiaoqiu; Dunlap, Kathrin A; Zhou, Beiyan; Johnson, Greg A; Wu, Guoyao

    2015-03-01

    Interferon tau (IFNT) was discovered as the pregnancy recognition signal in ruminants, but is now known to have a plethora of physiological functions in the mammalian uterus. The mammalian uterus includes, from the outer surface to the lumen, the serosa, myometrium and endometrium. The endometrium consists of the luminal, superficial glandular, and glandular epithelia, each with a unique phenotype, stromal cells, vascular elements, nerves and immune cells. The uterine epithelia secrete or selectively transport molecules into the uterine lumen that are collectively known as histotroph. Histotroph is required for growth and development of the conceptus (embryo and its associated extra-embryonic membranes) and includes nutrients such as amino acids and glucose, enzymes, growth factors, cytokines, lymphokines, transport proteins for vitamins and minerals and extracellular matrix molecules. Interferon tau and progesterone stimulate transport of amino acids in histotroph, particularly arginine. Arginine stimulates the mechanistic target of rapamycin pathway to induce proliferation, migration and protein synthesis by cells of the conceptus, and arginine is the substrate for synthesis of nitric oxide and polyamines required for growth and development of the conceptus. In ruminants, IFNT also acts in concert with progesterone from the corpus luteum to increase expression of genes for transport of nutrients into the uterine lumen, as well as proteases, protease inhibitors, growth factors for hematopoiesis and angiogenesis and other molecules critical for implantation and placentation. Collectively, the pleiotropic effects of IFNT contribute to survival, growth and development of the ruminant conceptus. PMID:25557050

  15. Stress-Induced Tau Phosphorylation: Functional Neuroplasticity or Neuronal Vulnerability?

    PubMed Central

    Rissman, Robert A.

    2010-01-01

    Abnormally phosphorylated tau protein is a key component of the pathology seen in neurodegenerative tauopathies, such as Alzheimer's disease (AD). Despite its association with disease, tau phosphorylation (tau-P) also plays an important role in neuroplasticity, such as dendritic/synaptic remodeling seen in the hippocampus in response to environmental challenges, such as stress. To define the boundaries between neuroplasticity and neuropathology, studies have attempted to characterize the paradigms, stimuli, and signaling intermediates involved in stress-induced tau-P. Supporting an involvement of stress in AD are data demonstrating alterations in stress pathways and peptides in the AD brain and epidemiological data implicating stress exposure as a risk factor for AD. In this review, the question of whether stress-induced tau-P can be used as a model for examining the relationship between functional neuroplasticity and neuronal vulnerability will be discussed. PMID:19584431

  16. Search for the Decay B+-->K+ tau-/+ mu+/-.

    PubMed

    Aubert, B; Bona, M; Boutigny, D; Karyotakis, Y; Lees, J P; Poireau, V; Prudent, X; Tisserand, V; Zghiche, A; Garra Tico, J; Grauges, E; Lopez, L; Palano, A; Pappagallo, M; Eigen, G; Stugu, B; Sun, L; Abrams, G S; Battaglia, M; Brown, D N; Button-Shafer, J; Cahn, R N; Groysman, Y; Jacobsen, R G; Kadyk, J A; Kerth, L T; Kolomensky, Yu G; Kukartsev, G; Lopes Pegna, D; Lynch, G; Mir, L M; Orimoto, T J; Osipenkov, I L; Ronan, M T; Tackmann, K; Tanabe, T; Wenzel, W A; del Amo Sanchez, P; Hawkes, C M; Watson, A T; Held, T; Koch, H; Pelizaeus, M; Schroeder, T; Steinke, M; Walker, D; Asgeirsson, D J; Cuhadar-Donszelmann, T; Fulsom, B G; Hearty, C; Mattison, T S; McKenna, J A; Khan, A; Saleem, M; 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; Bondioli, M; Curry, S; Eschrich, I; Kirkby, D; Lankford, A J; Lund, P; Mandelkern, M; Martin, E C; Stoker, D P; Abachi, S; Buchanan, C; Foulkes, S D; Gary, J W; Liu, F; Long, O; Shen, B C; Zhang, L; 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; Schalk, T; Schumm, B A; Seiden, A; Wilson, M G; Winstrom, L O; Chen, E; Cheng, C H; Fang, F; Hitlin, D G; Narsky, I; Piatenko, T; Porter, F C; Andreassen, R; 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; Smith, J G; Ulmer, K A; Wagner, S R; Zhang, J; Gabareen, A M; Soffer, A; Toki, W H; Wilson, R J; Winklmeier, F; Altenburg, D D; Feltresi, E; Hauke, A; Jasper, H; Merkel, J; Petzold, A; Spaan, B; Wacker, K; Klose, V; Kobel, M J; 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; Lombardo, V; Thiebaux, Ch; Verderi, M; Clark, P J; Gradl, W; Muheim, F; Playfer, S; Robertson, A I; Watson, J E; Xie, Y; Andreotti, M; Bettoni, D; Bozzi, C; Calabrese, R; Cecchi, A; Cibinetto, G; Franchini, P; Luppi, E; Negrini, M; Petrella, A; Piemontese, L; Prencipe, E; Santoro, V; 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; Chaisanguanthum, K S; Morii, M; Wu, J; Dubitzky, R S; Marks, J; Schenk, S; Uwer, U; Bard, D J; Dauncey, P D; Flack, R L; Nash, J A; Panduro Vazquez, W; Tibbetts, M; Behera, P K; Chai, X; Charles, M J; Mallik, U; Ziegler, V; 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; Lae, C K; Denig, A G; Fritsch, M; Schott, G; Arnaud, N; Béquilleux, J; D'Orazio, A; Davier, M; Grosdidier, G; Höcker, A; Lepeltier, V; Le Diberder, F; Lutz, A M; Pruvot, S; Rodier, S; Roudeau, P; Schune, M H; Serrano, J; Sordini, V; Stocchi, A; Wang, W F; Wormser, G; Lange, D J; Wright, D M; Bingham, I; Burke, J P; Chavez, C A; Forster, I J; Fry, J R; Gabathuler, E; Gamet, R; Hutchcroft, D E; Payne, D J; Schofield, K C; Touramanis, C; Bevan, A J; George, K A; Di Lodovico, F; Menges, W; Sacco, R; Cowan, G; Flaecher, H U; Hopkins, D A; Paramesvaran, S; 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; West, T J; Yi, J I; Anderson, J; Chen, C; Jawahery, A; Roberts, D A; Simi, G; Tuggle, J M; Blaylock, G; Dallapiccola, C; Hertzbach, S S; Li, X; Moore, T B; Salvati, E; Saremi, S; Cowan, R; Dujmic, D; Fisher, P H; Koeneke, K; Sciolla, G; Sekula, S J; Spitznagel, M; Taylor, F; Yamamoto, R K; Zhao, M; Zheng, Y; Mclachlin, S E; Patel, P M; Robertson, S H; Lazzaro, A; 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; De Nardo, G; Fabozzi, F; Lista, L; Monorchio, D; Sciacca, C; Baak, M A; Raven, G; Snoek, H L; Jessop, C P; Knoepfel, K J; LoSecco, J M; Benelli, G; Corwin, L A; Honscheid, K; Kagan, H; Kass, R; Morris, J P; Rahimi, A M; Regensburger, J 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; Gagliardi, N; Gaz, A; Margoni, M; Morandin, M; Pompili, A; Posocco, M; Rotondo, M; Simonetto, F; Stroili, R; Voci, C; Ben-Haim, E; Briand, H; Calderini, G; Chauveau, J; David, P; Del Buono, L; de la Vaissière, Ch; Hamon, O; Leruste, Ph; Malclès, J; Ocariz, J; Perez, A; Prendki, J; Gladney, L; Biasini, M; Covarelli, R; Manoni, E; Angelini, C; Batignani, G; Bettarini, S; Carpinelli, M; Cenci, R; Cervelli, A; 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; Biesiada, J; Elmer, P; Lau, Y P; Lu, C; Olsen, J; Smith, A J S; Telnov, A V; Baracchini, E; Bellini, F; Cavoto, G; del Re, D; Di Marco, E; Faccini, R; Ferrarotto, F; Ferroni, F; Gaspero, M; Jackson, P D; Gioi, L Li; Mazzoni, M A; Morganti, S; Piredda, G; Polci, F; Renga, F; Voena, C; Ebert, M; Hartmann, T; Schröder, H; Waldi, R; Adye, T; Castelli, G; Franek, B; Olaiya, E O; Ricciardi, S; Roethel, W; Wilson, F F; Emery, S; Escalier, M; Gaidot, A; Ganzhur, S F; Hamel de Monchenault, G; Kozanecki, W; 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; Dunwoodie, W; Field, R C; Glanzman, T; Gowdy, S J; Graham, M T; Grenier, P; Hast, C; Hryn'ova, T; Innes, W R; Kaminski, J; Kelsey, M H; Kim, H; Kim, P; Kocian, M L; 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; Ofte, I; 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; 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; 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; Krishnamurthy, M; Spanier, S M; Eckmann, R; Ritchie, J L; Ruland, A M; Schilling, C J; Schwitters, R F; Izen, J M; Lou, X C; Ye, S; Bianchi, F; Gallo, F; Gamba, D; Pelliccioni, M; Bomben, M; Bosisio, L; Cartaro, C; Cossutti, F; 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; Hamano, K; Kowalewski, R; Nugent, I M; Roney, J M; Sobie, R J; Harrison, P F; Ilic, J; Latham, T E; Mohanty, G B; Band, H R; Chen, X; Dasu, S; Flood, K T; Hollar, J J; Kutter, P E; Pan, Y; Pierini, M; Prepost, R; Wu, S L; Neal, H

    2007-11-16

    We present a search for the lepton flavor violating decay B+-->K+ tau-/+ mu+/- using 383 x 10;{6} BB[over ] events collected by the BABAR experiment. The branching fraction for this decay can be substantially enhanced in new physics models. The kinematics of the tau from the signal B decay are inferred from the K+, mu, and other B in the event, which is fully reconstructed in one of a variety of hadronic decay modes, allowing the signal B candidate to be fully reconstructed. We observe no excess of events over the expected background and set a limit of B(B+-->K+ tau mu)<7.7 x 10(-5) at 90% confidence level, where the branching fraction is for the sum of the K+ tau- mu+ and K+ tau+mu- final states. We use this result to improve a model-independent bound on the energy scale of flavor-changing new physics. PMID:18233132

  17. Tau co-organizes dynamic microtubule and actin networks

    PubMed Central

    Elie, Auréliane; Prezel, Elea; Guérin, Christophe; Denarier, Eric; Ramirez-Rios, Sacnicte; Serre, Laurence; Andrieux, Annie; Fourest-Lieuvin, Anne; Blanchoin, Laurent; Arnal, Isabelle

    2015-01-01

    The crosstalk between microtubules and actin is essential for cellular functions. However, mechanisms underlying the microtubule-actin organization by cross-linkers remain largely unexplored. Here, we report that tau, a neuronal microtubule-associated protein, binds to microtubules and actin simultaneously, promoting in vitro co-organization and coupled growth of both networks. By developing an original assay to visualize concomitant microtubule and actin assembly, we show that tau can induce guided polymerization of actin filaments along microtubule tracks and growth of single microtubules along actin filament bundles. Importantly, tau mediates microtubule-actin co-alignment without changing polymer growth properties. Mutagenesis studies further reveal that at least two of the four tau repeated motifs, primarily identified as tubulin-binding sites, are required to connect microtubules and actin. Tau thus represents a molecular linker between microtubule and actin networks, enabling a coordination of the two cytoskeletons that might be essential in various neuronal contexts. PMID:25944224

  18. CP violation tests for tau/top processes

    SciTech Connect

    Nelson, C.A.

    1994-12-31

    This paper reviews the following topics: tests for CP violation in top-quark production and decay processes. In particular, m{sub t} = 174 {plus_minus} 17 GeV implies good top-quark polarimetry because the W bosons in t-quark decays must be predominantly longitudinally polarized ({Gamma}{sub L}/{Gamma}{sub T} = 2.4). Tests for CP violation in tau lepton decays by the {tau} {yields} {rho}{nu} decay mode by usage of {rho} polarimetry signatures. Tests for complete measurement of the Z{sup 0},{gamma}* {yields} {tau}{sup {minus}}{tau}{sup +} vertex, including tests for CP violation in tau production processes.

  19. 14-3-3ζ Mediates Tau Aggregation in Human Neuroblastoma M17 Cells.

    PubMed

    Li, Tong; Paudel, Hemant K

    2016-01-01

    Microtubule-associated protein tau is the major component of paired helical filaments (PHFs) associated with the neuropathology of Alzheimer's disease (AD). Tau in the normal brain binds and stabilizes microtubules. Tau isolated from PHFs is hyperphosphorylated, which prevents it from binding to microtubules. Tau phosphorylation has been suggested to be involved in the development of NFT pathology in the AD brain. Recently, we showed that 14-3-3ζ is bound to tau in the PHFs and when incubated in vitro with 14-3-3ζ, tau formed amorphous aggregates, single-stranded straight filaments, double stranded ribbon-like filaments and PHF-like filaments that displayed close resemblance with corresponding ultrastructures of AD brain. Surprisingly however, phosphorylated and non-phosphorylated tau aggregated in a similar manner, indicating that tau phosphorylation does not affect in vitro tau aggregation (Qureshi et al (2013) Biochemistry 52, 6445-6455). In this study, we have examined the role of tau phosphorylation in tau aggregation in cellular level. We have found that in human M17 neuroblastoma cells, tau phosphorylation by GSK3β or PKA does not cause tau aggregation, but promotes 14-3-3ζ-induced tau aggregation by destabilizing microtubules. Microtubule disrupting drugs also promoted 14-3-3ζ-induced tau aggregation without changing tau phosphorylation in M17 cell. In vitro, when incubated with 14-3-3ζ and microtubules, nonphosphorylated tau bound to microtubules and did not aggregate. Phosphorylated tau on the other hand did not bind to microtubules and aggregated. Our data indicate that microtubule-bound tau is resistant to 14-3-3ζ-induced tau aggregation and suggest that tau phosphorylation promotes tau aggregation in the brain by detaching tau from microtubules and thus making it accessible to 14-3-3ζ. PMID:27548710

  20. 14-3-3ζ Mediates Tau Aggregation in Human Neuroblastoma M17 Cells

    PubMed Central

    Li, Tong; Paudel, Hemant K.

    2016-01-01

    Microtubule-associated protein tau is the major component of paired helical filaments (PHFs) associated with the neuropathology of Alzheimer’s disease (AD). Tau in the normal brain binds and stabilizes microtubules. Tau isolated from PHFs is hyperphosphorylated, which prevents it from binding to microtubules. Tau phosphorylation has been suggested to be involved in the development of NFT pathology in the AD brain. Recently, we showed that 14-3-3ζ is bound to tau in the PHFs and when incubated in vitro with 14-3-3ζ, tau formed amorphous aggregates, single-stranded straight filaments, double stranded ribbon-like filaments and PHF-like filaments that displayed close resemblance with corresponding ultrastructures of AD brain. Surprisingly however, phosphorylated and non-phosphorylated tau aggregated in a similar manner, indicating that tau phosphorylation does not affect in vitro tau aggregation (Qureshi et al (2013) Biochemistry 52, 6445–6455). In this study, we have examined the role of tau phosphorylation in tau aggregation in cellular level. We have found that in human M17 neuroblastoma cells, tau phosphorylation by GSK3β or PKA does not cause tau aggregation, but promotes 14-3-3ζ-induced tau aggregation by destabilizing microtubules. Microtubule disrupting drugs also promoted 14-3-3ζ-induced tau aggregation without changing tau phosphorylation in M17 cell. In vitro, when incubated with 14-3-3ζ and microtubules, nonphosphorylated tau bound to microtubules and did not aggregate. Phosphorylated tau on the other hand did not bind to microtubules and aggregated. Our data indicate that microtubule-bound tau is resistant to 14-3-3ζ-induced tau aggregation and suggest that tau phosphorylation promotes tau aggregation in the brain by detaching tau from microtubules and thus making it accessible to 14-3-3ζ. PMID:27548710

  1. Characterization of two VQIXXK motifs for tau fibrillization in vitro.

    PubMed

    Li, Wenkai; Lee, Virginia M-Y

    2006-12-26

    Tau proteins are building blocks of the filaments that form neurofibrillary tangles of Alzheimer's disease (AD) and related neurodegenerative tauopathies. It was recently reported that two VQIXXK motifs in the microtubule (MT) binding region, named PHF6 and PHF6*, are responsible for tau fibrillization. However, the exact role each of these motifs plays in this process has not been analyzed in detail. Using a recombinant human tau fragment containing only the four MT-binding repeats (K18), we show that deletion of either PHF6 or PHF6* affected tau assembly but only PHF6 is essential for filament formation, suggesting a critical role of this motif. To determine the amino acid residues within PHF6 that are required for tau fibrillization, a series of deletion and mutation constructs targeting this motif were generated. Deletion of VQI in either PHF6 or PHF6* lessened but did not eliminate K18 fibrillization. However, removal of the single K311 residue from PHF6 completely abrogated the fibril formation of K18. K311D mutation of K18 inhibited tau filament formation, while K311A and K311R mutations had no effect. These data imply that charge change at position 311 is important in tau fibril formation. A similar requirement of nonnegative charge at this position for fibrillization was observed with the full-length human tau isoform (T40), and data from these studies indicate that the formation of fibrils by T40K311D and T40K311P mutants is repressed at the nucleation phase. These findings provide important insights into the mechanisms of tau fibrillization and suggest targets for AD drug discovery to ameliorate neurodegeneration mediated by filamentous tau pathologies.

  2. Evidence for B{sup -{yields}{tau}-{nu}}{sub {tau}}with a semileptonic tagging method

    SciTech Connect

    Hara, K.; Iijima, T.; Hayasaka, K.; Inami, K.; Miyazaki, Y.; Mori, T.; Ohshima, T.; Senyo, K.; Aihara, H.; Aulchenko, V.; Bondar, A.; Eidelman, S.; Gabyshev, N.; Kuzmin, A.; Shwartz, B.; Zhilich, V.; Zyukova, O.; Aushev, T.; Aziz, T.; Mohanty, G. B.

    2010-10-01

    We present a measurement of the decay B{sup -{yields}{tau}-{nu}}{sub {tau}}using a data sample containing 657x10{sup 6} BB pairs collected at the {Upsilon}(4S) resonance with the Belle detector at the KEKB asymmetric-energy e{sup +}e{sup -} collider. A sample of B{sup +}B{sup -} pairs are tagged by reconstructing one B{sup +} meson decaying semileptonically. We detect the B{sup -{yields}{tau}-{nu}}{sub {tau}}candidate in the recoil. We obtain a signal with a significance of 3.6 standard deviations including systematic uncertainties, and measure the branching fraction to be B(B{sup -{yields}{tau}-{nu}}{sub {tau}})=[1.54{sub -0.37}{sup +0.38}(stat){sub -0.31}{sup +0.29}(syst)]x10{sup -4}. This result confirms the evidence for B{sup -{yields}{tau}-{nu}}{sub {tau}}obtained in a previous Belle measurement that used a hadronic B tagging method.

  3. Measurement of the Semileptonic B-bar->D{sup (*)}{tau}{nu}-bar{sub {tau}} Decays at BABAR

    SciTech Connect

    Lopes Pegna, David

    2010-02-10

    Semileptonic B meson decays into final states containing the tau lepton are of interesting as they provide information on the Standard Model as well as a window on new physics effects. We present results on B-bar->D{sup (*)}taunu-bar{sub tau} decays where the second B in the event is fully reconstructed.

  4. Development of a Scalable, High-Throughput-Compatible Assay to Detect Tau Aggregates Using iPSC-Derived Cortical Neurons Maintained in a Three-Dimensional Culture Format.

    PubMed

    Medda, X; Mertens, L; Versweyveld, S; Diels, A; Barnham, L; Bretteville, A; Buist, A; Verheyen, A; Royaux, I; Ebneth, A; Cabrera-Socorro, A

    2016-09-01

    Tau aggregation is the pathological hallmark that best correlates with the progression of Alzheimer's disease (AD). The presence of neurofibrillary tangles (NFTs), formed of hyperphosphorylated tau, leads to neuronal dysfunction and loss, and is directly associated with the cognitive decline observed in AD patients. The limited success in targeting β-amyloid pathologies has reinforced the hypothesis of blocking tau phosphorylation, aggregation, and/or spreading as alternative therapeutic entry points to treat AD. Identification of novel therapies requires disease-relevant and scalable assays capable of reproducing key features of the pathology in an in vitro setting. Here we use induced pluripotent stem cells (iPSCs) as a virtually unlimited source of human cortical neurons to develop a robust and scalable tau aggregation model compatible with high-throughput screening (HTS). We downscaled cell culture conditions to 384-well plate format and used Matrigel to introduce an extra physical protection against cell detachment that reduces shearing stress and better recapitulates pathological conditions. We complemented the assay with AlphaLISA technology for the detection of tau aggregates in a high-throughput-compatible format. The assay is reproducible across users and works with different commercially available iPSC lines, representing a highly translational tool for the identification of novel treatments against tauopathies, including AD. PMID:26984927

  5. Overexpression of Wild-Type Murine Tau Results in Progressive Tauopathy and Neurodegeneration

    PubMed Central

    Adams, Stephanie J.; Crook, Richard J.P.; DeTure, Michael; Randle, Suzanne J.; Innes, Amy E.; Yu, Xin Z.; Lin, Wen-Lang; Dugger, Brittany N.; McBride, Melinda; Hutton, Mike; Dickson, Dennis W.; McGowan, Eileen

    2009-01-01

    Here, we describe the generation and characterization of a novel tau transgenic mouse model (mTau) that overexpresses wild-type murine tau protein by twofold compared with endogenous levels. Transgenic tau expression was driven by a BAC transgene containing the entire wild-type mouse tau locus, including the endogenous promoter and the regulatory elements associated with the tau gene. The mTau model therefore differs from other tau models in that regulation of the genomic mouse transgene mimics that of the endogenous gene, including normal exon splicing regulation. Biochemical data from the mTau mice demonstrated that modest elevation of mouse tau leads to tau hyperphosphorylation at multiple pathologically relevant epitopes and accumulation of sarkosyl-insoluble tau. The mTau mice show a progressive increase in hyperphosphorylated tau pathology with age up to 15 to 18 months, which is accompanied by gliosis and vacuolization. In contrast, older mice show a decrease in tau pathology levels, which may represent hippocampal neuronal loss occurring in this wild-type model. Collectively, these results describe a novel model of tauopathy that develops pathological changes reminiscent of early stage Alzheimer’s disease and other related neurodegenerative diseases, achieved without overexpression of a mutant human tau transgene. This model will provide an important tool for understanding the early events leading to the development of tau pathology and a model for analysis of potential therapeutic targets for sporadic tauopathies. PMID:19717642

  6. Porcine MAP3K5 analysis: molecular cloning, characterization, tissue expression pattern, and copy number variations associated with residual feed intake.

    PubMed

    Pu, L; Zhang, L C; Zhang, J S; Song, X; Wang, L G; Liang, J; Zhang, Y B; Liu, X; Yan, H; Zhang, T; Yue, J W; Li, N; Wu, Q Q; Wang, L X

    2016-01-01

    Mitogen-activated protein kinase kinase kinase 5 (MAP3K5) is essential for apoptosis, proliferation, differentiation, and immune responses, and is a candidate marker for residual feed intake (RFI) in pig. We cloned the full-length cDNA sequence of porcine MAP3K5 by rapid-amplification of cDNA ends. The 5451-bp gene contains a 5'-untranslated region (UTR) (718 bp), a coding region (3738 bp), and a 3'-UTR (995 bp), and encodes a peptide of 1245 amino acids, which shares 97, 99, 97, 93, 91, and 84% sequence identity with cattle, sheep, human, mouse, chicken, and zebrafish MAP3K5, respectively. The deduced MAP3K5 protein sequence contains two conserved domains: a DUF4071 domain and a protein kinase domain. Phylogenetic analysis showed that porcine MAP3K5 forms a separate branch to vicugna and camel MAP3K5. Tissue expression analysis using real-time quantitative polymerase chain reaction (qRT-PCR) revealed that MAP3K5 was expressed in the heart, liver, spleen, lung, kidney, muscle, fat, pancrea, ileum, and stomach tissues. Copy number variation was detected for porcine MAP3K5 and validated by qRT-PCR. Furthermore, a significant increase in average copy number was detected in the low RFI group when compared to the high RFI group in a Duroc pig population. These results provide useful information regarding the influence of MAP3K5 on RFI in pigs. PMID:27525933

  7. Histone deacetylase 6 inhibition improves memory and reduces total tau levels in a mouse model of tau deposition

    PubMed Central

    2014-01-01

    Introduction Tau pathology is associated with a number of age-related neurodegenerative disorders. Few treatments have been demonstrated to diminish the impact of tau pathology in mouse models and none are yet effective in humans. Histone deacetylase 6 (HDAC6) is an enzyme that removes acetyl groups from cytoplasmic proteins, rather than nuclear histones. Its substrates include tubulin, heat shock protein 90 and cortactin. Tubastatin A is a selective inhibitor of HDAC6. Modification of tau pathology by specific inhibition of HDAC6 presents a potential therapeutic approach in tauopathy. Methods We treated rTg4510 mouse models of tau deposition and non-transgenic mice with tubastatin (25 mg/kg) or saline (0.9%) from 5 to 7 months of age. Cognitive behavior analysis, histology and biochemical analysis were applied to access the effect of tubastatin on memory, tau pathology and neurodegeneration (hippocampal volume). Results We present data showing that tubastatin restored memory function in rTg4510 mice and reversed a hyperactivity phenotype. We further found that tubastatin reduced the levels of total tau, both histologically and by western analysis. Reduction in total tau levels was positively correlated with memory improvement in these mice. However, there was no impact on phosphorylated forms of tau, either by histology or western analysis, nor was there an impact on silver positive inclusions histologically. Conclusion Potential mechanisms by which HDAC6 inhibitors might benefit the rTg4510 mouse include stabilization of microtubules secondary to increased tubulin acetylation, increased degradation of tau secondary to increased acetylation of HSP90 or both. These data support the use of HDAC6 inhibitors as potential therapeutic agents against tau pathology. PMID:24576665

  8. Hadron structure in {tau}{yields}KK{pi}{nu}{sub {tau}}decays

    SciTech Connect

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

    2010-02-01

    We analyze the hadronization structure of both vector and axial-vector currents leading to {tau}{yields}KK{pi}{nu}{sub {tau}}decays. At leading order in the 1/N{sub C} expansion, and considering only the contribution of the lightest resonances, we work out, within the framework of the resonance chiral Lagrangian, the structure of the local vertices involved in those processes. The couplings in the resonance theory are constrained by imposing the asymptotic behavior of vector and axial-vector spectral functions ruled by QCD. In this way we predict the hadron spectra and conclude that, contrary to previous assertions, the vector contribution dominates by far over the axial-vector one in all KK{pi} charge channels.

  9. First measurement of sigma (p anti-p ---> Z) . Br (Z ---> tau tau) at s**(1/2) = 1.96- TeV

    SciTech Connect

    Abazov, V.M.; Abbott, B.; Abolins, M.; Acharya, B.S.; Adams, M.; Adams, T.; Agelou, M.; Agram, J.-L.; Ahn, S.H.; Ahsan, M.; Alexeev, G.D.; Alkhazov, G.; Alton, A.; Alverson, G.; Alves, G.A.; Anastasoaie, M.; Andeen, T.; Anderson, S.; Andrieu, B.; Arnoud, Y.; Askew, A.; /Buenos Aires U. /Rio de Janeiro, CBPF /Rio de Janeiro State U. /Sao Paulo, IFT /Alberta U. /Simon Fraser U. /York U., Canada /McGill U. /Beijing, Inst. High Energy Phys. /Andes U., Bogota /Charles U. /Prague, Tech. U. /Prague, Inst. Phys. /San Francisco de Quito U. /Clermont-Ferrand U. /LPSC, Grenoble /Marseille, CPPM /Orsay, LAL /Paris U., VI-VII /DAPNIA, Saclay /Strasbourg, IReS

    2004-12-01

    The authors present a measurement of the cross section for Z production times the branching fraction to {tau} leptons, {sigma} {center_dot} Br(Z {yields} {tau}{sup +}{tau}{sup -}), in p{bar p} collisions at {radical}s = 1.96 TeV in the channel in which one {tau} decays into {mu}{nu}{sub {mu}}{nu}{sub {tau}}, and the other into hadrons + {nu}{sub {tau}} or e{nu}{sub e}{nu}{sub {tau}}. The data sample corresponds to an integrated luminosity of 226 pb{sup -1} collected with the D0 detector at the Fermilab Tevatron collider. The final sample contains 2008 candidate events with an estimated background of 55%. From this they obtain {sigma} {center_dot} Br(Z {yields} {tau}{sup +}{tau}{sup -}) = 237 {+-} 15(stat) {+-} 18(sys) {+-} 15(lum) pb, in agreement with the standard model prediction.

  10. CP Violation in Tau to K* Decays

    SciTech Connect

    Hodgkinson, Mark; /Manchester U.

    2006-03-10

    A sample of {tau}{sup {+-}} {yields} K*{sup {+-}} decays with K*{sup {+-}} {yields} K{sub S}{sup 0}{pi}{sup {+-}} and K{sub S}{sup 0} {yields} {pi}{sup +}{pi}{sup -}, using 123.4 fb{sup -1} of data collected by the BaBar detector at the Stanford Linear Accelerator Center, is used to search for a direct CP violation effect in the charged Higgs sector. No evidence of CP violation is found and the imaginary part of the charged Higgs coupling, {l_brace}Im{r_brace}({Lambda}), in the Multi-Higgs-Doublet-Model is found to be at -0.284 < {l_brace}Im{r_brace}({Lambda}) < 0.200 at 90% Confidence Level. In addition the installation of the kk2f Monte Carlo generator into the BaBar software framework is described.

  11. Deep photospheric flows in Tau Scorpii

    NASA Technical Reports Server (NTRS)

    Smith, M. A.; Karp, A. H.

    1979-01-01

    From analysis of weak, unblended, ultraviolet lines observed in Tau Scorpii by Copernicus, the same line widths and the same slightly blue-depressed wings as found in the upper photospheric lines of the visual region are found. In addition, a radial-velocity discrepancy of about 6 km/s between weak and strong lines in the 1000-1300-A region is found. These results are in quantitative agreement with one another and with the results of the visual region. They imply that a flow of material is present even in the deep photosphere of this star. However, one cannot yet specify the geometry of the flow (outward-radial versus temperature-weighted convection columns). At the least, this flow alters the expected radiation-driven flow solution close to the photosphere. At the most, it could provide the heating of a chromosphere or a corona just outside the photosphere, as required by the imperfect flow model.

  12. H4K5 histone acetylation of BRG1 is associated with heroin administration rather than addiction

    PubMed Central

    Xu, Limin; Hong, Qingxiao; Chen, Xiaoying; Xu, Xuting; Liu, Huifen; Zhou, Wenhua; Duan, Shiwei

    2016-01-01

    Diacetylmorphine hydrochloride (heroin) addiction is a chronic relapsing brain disorder that is a heavy public health burden worldwide. Brm/SWI2-related gene-1 (BRG1) is a tumor suppressor gene that can influence embryogenesis and the development of the cerebellum. The current study aimed to investigate the effect of histone H4 lysine 5 (H4K5) modifications on the BRG1 gene in brain tissue of the ventral tegmental area (VTA) of heroin-addicted rats. A total of 21 male Sprague Dawley rats were raised in a standard manner and underwent heroin self-administration training. Rats were randomly divided into three equal groups: Group A, self-administered delivery of heroin; group B, yoked delivery of heroin; and group C, yoked delivery of saline. The VTA was harvested and subjected to chromatin immunoprecipitation (ChIP) analysis. Gene expression was evaluated by quantitative polymerase chain reaction. We calculated the recovery rate, which indicated the percentage of the total input BRG1 recovered by ChIP. Our results showed that BRG1 was less associated with H4K5 histone modification in the group of rats that underwent heroin self-administration than in the other two groups (A vs. B, P=0.031; A vs. C, P=0.067). The recovery fold changes of the self-administration group and the passive-administration group were significantly different from those of the group with yoked saline (A vs. C, P=0.013; B vs. C, P=0.009; A vs. B, P=0.731). The results of the current study demonstrated that H4K5 histone acetylation of BRG1 in the VTA may be associated with heroin administration, but not addiction. PMID:27588112

  13. LRRK2 Promotes Tau Accumulation, Aggregation and Release.

    PubMed

    Guerreiro, Patrícia Silva; Gerhardt, Ellen; Lopes da Fonseca, Tomás; Bähr, Mathias; Outeiro, Tiago Fleming; Eckermann, Katrin

    2016-07-01

    Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are known as the most frequent cause of familial Parkinson's disease (PD), but are also present in sporadic cases. The G2019S-LRRK2 mutation is located in the kinase domain of the protein, and has consistently been reported to promote a gain of kinase function. Several proteins have been reported as LRRK2 substrates and/or interactors, suggesting possible pathways involved in neurodegeneration in PD. Hyperphosphorylated Tau protein accumulates in neurofibrillary tangles, a typical pathological hallmark in Alzheimer's disease and frontotemporal dementia. In addition, it is also frequently found in the brains of PD patients. Although LRRK2 is a kinase, it appears that a putative interaction with Tau is phosphorylation-independent. However, the underlying mechanisms and the cellular consequences of this interaction are still unclear. In this study, we demonstrate an interaction between LRRK2 and Tau and that LRRK2 promotes the accumulation of non-monomeric and high-molecular weight (HMW) Tau species independent of its kinase activity. Interestingly, we found that LRRK2 increases Tau secretion, possibly as a consequence of an impairment of Tau proteasomal degradation. Our data highlight a mechanism through which LRRK2 regulates intracellular Tau levels, contributing to the progression of the pathology caused by the LRRK2-mediated proteasome impairment. In total, our findings suggest that the interplay between LRRK2 and proteasome activity might constitute a valid target for therapeutic intervention in PD.

  14. Measurement of the Tau- to F1(1285) Pi- Nu/Tau Branching Fraction And a Search for Second-Class Currents in Tau to Eta-Prime(958) Pi- Nu/Tau

    SciTech Connect

    Alwyn, K.E.; /Manchester U.

    2011-12-01

    The {tau}{sup -} {yields} {eta}{pi}{sup -}{pi}+{pi}{sup -}{nu}{tau} decay with the {eta} {yields} {gamma}{gamma} mode is studied using 384 fb{sup -1} of data collected by the BaBar detector. The branching fraction is measured to be (1.60 {+-} 0.05 {+-} 0.11) x 10{sup -4}. It is found that {tau}{sup -} {yields} f1(1285){pi}{sup -}{nu}{tau} {yields} {eta}{pi}{sup -}{pi}+{pi}{sup -}{nu}{tau} is the dominant decay mode with a branching fraction of (1.11 {+-} 0.06 {+-} 0.05) x 10{sup -4}. The first error is statistical and the second systematic. In addition, a 90% confidence level upper limit on the branching fraction of the {tau}{sup -} {yields} {eta}{prime}(958){pi}{sup -}{nu}{tau} decay is measured to be 7.2 x 10{sup -6}. This last decay proceeds through a second-class current and is expected to be forbidden in the limit of isospin symmetry.

  15. Effects of macromolecular crowding and osmolyte on human Tau fibrillation.

    PubMed

    Wu, Yingying; Teng, Ningning; Li, Sen

    2016-09-01

    Tau fibrillation is reported to be involved in neurodegenerative disorders, such as Alzheimer's disease, in which the natural environment is very crowded in the cells. Understanding the role of crowding environments in regulating Tau fibrillation is of great importance for elucidating the etiology of these diseases. In this experiment, the effects of macromolecular crowding and osmolyte reagents in the crowding environment on Tau fibrillation were studied by thioflavin T binding, SDS-PAGE and TEM assays. Ficoll 70 and Dextran 70 of different concentrations were used as macromolecular crowding reagents inside the cells and showed a strong enhancing effect on the fibrillation of normal and hyperphosphorylated Tau. The enhancing effect of Dextran is stronger than that of Ficoll 70 at the same concentration. In addition, the cellular osmolyte sucrose was found to protect Tau against fibrillation, and inhibit the enhancing effect of macromolecular crowding on Tau fibrillation. A possible model for the fibrillation process of Tau and the effect of macromolecular crowding and osmolyte on this process was proposed based on these experimental results. The information obtained from our study can enhance the understanding of how proteins aggregate and avoid aggregation in crowded physiological environments and might lead to a better understanding of the molecular mechanisms of Alzheimer's disease in vivo.

  16. Measurement of the tau- to eta pi-pi+pi-nu tau Branching Fraction and a Search for a Second-Class Current in the tau- to eta'(958)pi-nu tau Decay

    SciTech Connect

    Aubert, B.; Bona, M.; Boutigny, D.; Karyotakis, Y.; Lees, J.P.; Poireau, V.; Prudent, X.; Tisserand, V.; Zghiche, A.; Garra Tico, J.; Grauges, E.; Lopez, L.; Palano, A.; Pappagallo, M.; Eigen, G.; Stugu, B.; Sun, L.; Abrams, G.S.; Battaglia, M.; Brown, David Nathan; Button-Shafer, J.; /LBL, Berkeley /UC, Berkeley /Birmingham U. /Ruhr U., Bochum /Bristol U. /British Columbia U. /Brunel U. /Novosibirsk, IYF /UC, Irvine /UCLA /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. /Ferrara U. /Frascati /Genoa U. /Harvard U. /Heidelberg U. /Imperial Coll., London /Iowa U. /Iowa State U. /Johns Hopkins U. /Karlsruhe U. /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. /Naples U. /NIKHEF, Amsterdam /Notre Dame U. /Ohio State U. /Oregon U. /Padua U. /Paris U., VI-VII /Pennsylvania U. /Perugia U. /Pisa U. /Princeton U. /INFN, Rome /Rostock U. /Rutherford /DSM, DAPNIA, Saclay /South Carolina U. /SLAC /Stanford U., Phys. Dept. /SUNY, Albany /Tennessee U. /Texas U. /Texas U., Dallas /Turin U. /INFN, Turin /Trieste U. /Valencia U., IFIC /Victoria U. /Warwick U. /Wisconsin U., Madison /Yale U.

    2008-03-24

    The {tau}{sup -} {yields} {eta}{pi}{sup -}{pi}{sup +}{pi}{sup -}{nu}{sub {tau}} decay with the {eta} {yields} {gamma}{gamma} mode is studied using 384 fb{sup -1} of data collected by the BABAR detector. The branching fraction is measured to be (1.60 {+-} 0.05 {+-} 0.11) x 10{sup -4}. It is found that {tau}{sup -} {yields} f{sub 1}(1285){pi}{sup -} {nu}{sub {tau}} {yields} {eta}{pi}{sup -}{pi}{sup +}{pi}{sup -}{nu}{sub {tau}} is the dominant decay mode with a branching fraction of (1.11 {+-} 0.06 {+-} 0.05) x 10{sup -4}. The first error on the branching fractions is statistical and the second systematic. In addition, a 90% confidence level upper limit on the branching fraction of the {tau}{sup -} {yields} {eta}{prime}(958){pi}{sup -}{nu}{sub {tau}} decay is measured to be 7.2 x 10{sup -6}. This last decay proceeds through a second-class current and is expected to be forbidden in the limit of isospin symmetry.

  17. Aging-related tau astrogliopathy (ARTAG): harmonized evaluation strategy.

    PubMed

    Kovacs, Gabor G; Ferrer, Isidro; Grinberg, Lea T; Alafuzoff, Irina; Attems, Johannes; Budka, Herbert; Cairns, Nigel J; Crary, John F; Duyckaerts, Charles; Ghetti, Bernardino; Halliday, Glenda M; Ironside, James W; Love, Seth; Mackenzie, Ian R; Munoz, David G; Murray, Melissa E; Nelson, Peter T; Takahashi, Hitoshi; Trojanowski, John Q; Ansorge, Olaf; Arzberger, Thomas; Baborie, Atik; Beach, Thomas G; Bieniek, Kevin F; Bigio, Eileen H; Bodi, Istvan; Dugger, Brittany N; Feany, Mel; Gelpi, Ellen; Gentleman, Stephen M; Giaccone, Giorgio; Hatanpaa, Kimmo J; Heale, Richard; Hof, Patrick R; Hofer, Monika; Hortobágyi, Tibor; Jellinger, Kurt; Jicha, Gregory A; Ince, Paul; Kofler, Julia; Kövari, Enikö; Kril, Jillian J; Mann, David M; Matej, Radoslav; McKee, Ann C; McLean, Catriona; Milenkovic, Ivan; Montine, Thomas J; Murayama, Shigeo; Lee, Edward B; Rahimi, Jasmin; Rodriguez, Roberta D; Rozemüller, Annemieke; Schneider, Julie A; Schultz, Christian; Seeley, William; Seilhean, Danielle; Smith, Colin; Tagliavini, Fabrizio; Takao, Masaki; Thal, Dietmar Rudolf; Toledo, Jon B; Tolnay, Markus; Troncoso, Juan C; Vinters, Harry V; Weis, Serge; Wharton, Stephen B; White, Charles L; Wisniewski, Thomas; Woulfe, John M; Yamada, Masahito; Dickson, Dennis W

    2016-01-01

    Pathological accumulation of abnormally phosphorylated tau protein in astrocytes is a frequent, but poorly characterized feature of the aging brain. Its etiology is uncertain, but its presence is sufficiently ubiquitous to merit further characterization and classification, which may stimulate clinicopathological studies and research into its pathobiology. This paper aims to harmonize evaluation and nomenclature of aging-related tau astrogliopathy (ARTAG), a term that refers to a morphological spectrum of astroglial pathology detected by tau immunohistochemistry, especially with phosphorylation-dependent and 4R isoform-specific antibodies. ARTAG occurs mainly, but not exclusively, in individuals over 60 years of age. Tau-immunoreactive astrocytes in ARTAG include thorn-shaped astrocytes at the glia limitans and in white matter, as well as solitary or clustered astrocytes with perinuclear cytoplasmic tau immunoreactivity that extends into the astroglial processes as fine fibrillar or granular immunopositivity, typically in gray matter. Various forms of ARTAG may coexist in the same brain and might reflect different pathogenic processes. Based on morphology and anatomical distribution, ARTAG can be distinguished from primary tauopathies, but may be concurrent with primary tauopathies or other disorders. We recommend four steps for evaluation of ARTAG: (1) identification of five types based on the location of either morphologies of tau astrogliopathy: subpial, subependymal, perivascular, white matter, gray matter; (2) documentation of the regional involvement: medial temporal lobe, lobar (frontal, parietal, occipital, lateral temporal), subcortical, brainstem; (3) documentation of the severity of tau astrogliopathy; and (4) description of subregional involvement. Some types of ARTAG may underlie neurological symptoms; however, the clinical significance of ARTAG is currently uncertain and awaits further studies. The goal of this proposal is to raise awareness of

  18. Adaptive deployment of model reductions for tau-leaping simulation

    NASA Astrophysics Data System (ADS)

    Wu, Sheng; Fu, Jin; Petzold, Linda R.

    2015-05-01

    Multiple time scales in cellular chemical reaction systems often render the tau-leaping algorithm inefficient. Various model reductions have been proposed to accelerate tau-leaping simulations. However, these are often identified and deployed manually, requiring expert knowledge. This is time-consuming and prone to error. In previous work, we proposed a methodology for automatic identification and validation of model reduction opportunities for tau-leaping simulation. Here, we show how the model reductions can be automatically and adaptively deployed during the time course of a simulation. For multiscale systems, this can result in substantial speedups.

  19. Adaptive deployment of model reductions for tau-leaping simulation

    PubMed Central

    Fu, Jin; Petzold, Linda R.

    2015-01-01

    Multiple time scales in cellular chemical reaction systems often render the tau-leaping algorithm inefficient. Various model reductions have been proposed to accelerate tau-leaping simulations. However, these are often identified and deployed manually, requiring expert knowledge. This is time-consuming and prone to error. In previous work, we proposed a methodology for automatic identification and validation of model reduction opportunities for tau-leaping simulation. Here, we show how the model reductions can be automatically and adaptively deployed during the time course of a simulation. For multiscale systems, this can result in substantial speedups. PMID:26026435

  20. A measurement of the tau lepton lifetime at ARGUS

    NASA Astrophysics Data System (ADS)

    Saull, Patrick Richard Behrendt

    Data taken with the ARGUS detector at DESY, Hamburg, specifically toverlinetoverline pairs produced from e+e - collisions in the energy range (10.4-10.6)GeV, are used to make a precision measurement of the tau lifetime. A new method is introduced which is independent of the beam position and envelope, and applicable to tau events having one-three topology. Applied to ARGUS data the method yields a value for the tau lifetime of tt=287+/-11(st atistical)+/-8(systemat ic)fs.

  1. Search for lepton flavor violating decays tau+/--->l+/-omega.

    PubMed

    Aubert, B; Bona, M; Karyotakis, Y; Lees, J P; Poireau, V; Prudent, X; Tisserand, V; Zghiche, A; Garra Tico, J; Grauges, E; Lopez, L; Palano, A; Pappagallo, M; Eigen, G; Stugu, B; Sun, L; Abrams, G S; Battaglia, M; Brown, D N; Button-Shafer, J; Cahn, R N; Jacobsen, R G; Kadyk, J A; Kerth, L T; Kolomensky, Yu G; Kukartsev, G; Lopes Pegna, D; Lynch, G; Orimoto, T J; Osipenkov, I L; Ronan, M T; Tackmann, K; Tanabe, T; Wenzel, W A; Del Amo Sanchez, P; Hawkes, C M; Soni, N; Watson, A T; Koch, H; Schroeder, T; Walker, D; Asgeirsson, D J; Cuhadar-Donszelmann, T; Fulsom, B G; Hearty, C; Mattison, T S; McKenna, J A; Barrett, M; Khan, A; Saleem, M; Teodorescu, L; 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; Abachi, S; Buchanan, C; Gary, J W; Liu, F; Long, O; Shen, B C; Vitug, G M; Zhang, L; 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; Schalk, T; Schumm, B A; Seiden, A; Wilson, M G; Winstrom, L O; Chen, E; Cheng, C H; 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; Blanc, F; Bloom, P C; Ford, W T; Hirschauer, J F; Kreisel, A; Nagel, M; Nauenberg, U; Olivas, A; Smith, J G; Ulmer, K A; Wagner, S R; Zhang, J; Ayad, R; Gabareen, A M; Soffer, A; Toki, W H; Wilson, R J; Altenburg, D D; Feltresi, E; Hauke, A; Jasper, H; Merkel, J; Petzold, A; Spaan, B; Wacker, K; Klose, V; Kobel, M J; 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; Lombardo, V; Thiebaux, Ch; Verderi, M; Clark, P J; Gradl, W; Muheim, F; Playfer, S; Robertson, A I; Watson, J E; Xie, Y; Andreotti, M; Bettoni, D; Bozzi, C; Calabrese, R; Cecchi, A; Cibinetto, G; Franchini, P; Luppi, E; Negrini, M; Petrella, A; Piemontese, L; Prencipe, E; Santoro, V; 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; Chaisanguanthum, K S; Morii, M; Wu, J; Dubitzky, R S; Marks, J; Schenk, S; Uwer, U; Bard, D J; Dauncey, P D; Nash, J A; Panduro Vazquez, W; Tibbetts, M; Behera, P K; Chai, X; 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; Lae, C K; Denig, A G; Fritsch, M; Schott, G; Arnaud, N; Béquilleux, J; D'Orazio, A; Davier, M; Grosdidier, G; Höcker, A; Lepeltier, V; Le Diberder, F; Lutz, A M; Pruvot, S; Roudeau, P; Schune, M H; Serrano, J; Sordini, V; Stocchi, A; Wang, W F; 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; Schofield, K C; Touramanis, C; Bevan, A J; George, K A; Di Lodovico, F; Sacco, R; Cowan, G; Flaecher, H U; Hopkins, D A; Paramesvaran, S; Salvatore, F; Wren, A C; Brown, D N; Davis, C L; Barlow, N R; Barlow, R J; Chia, Y M; Edgar, C L; 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; Hertzbach, S S; Li, X; Moore, T B; Salvati, E; Saremi, S; Cowan, R; Dujmic, D; Fisher, P H; Koeneke, K; Sciolla, G; Spitznagel, M; Taylor, F; Yamamoto, R K; Zhao, M; McLachlin, S E; Patel, P M; Robertson, S H; Lazzaro, A; 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; De Nardo, G; Fabozzi, F; Lista, L; Monorchio, D; Sciacca, C; Baak, M A; Raven, G; Snoek, H L; Jessop, C P; Knoepfel, K J; Losecco, J M; Benelli, G; 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; Gagliardi, N; Gaz, A; Margoni, M; Morandin, M; Pompili, A; Posocco, M; Rotondo, M; Simonetto, F; Stroili, R; Voci, C; Ben-Haim, E; Briand, H; Calderini, G; Chauveau, J; David, P; Del Buono, L; de la Vaissière, Ch; Hamon, O; Leruste, Ph; Malclès, J; Ocariz, J; Perez, A; Prendki, J; Gladney, L; Biasini, M; Covarelli, R; Manoni, E; Angelini, C; Batignani, G; Bettarini, S; Carpinelli, M; Cenci, R; Cervelli, A; Forti, F; Giorgi, M A; Lusiani, A; Marchiori, G; Mazur, M A; Morganti, M; Neri, N; Paoloni, E; Rizzo, G; Walsh, J J; Biesiada, J; Lau, Y P; Lu, C; Olsen, J; Smith, A J S; Telnov, A V; Baracchini, E; Bellini, F; Cavoto, G; Del Re, D; Di Marco, E; Faccini, R; Ferrarotto, F; Ferroni, F; Gaspero, M; Jackson, P D; Mazzoni, M A; Morganti, S; Piredda, G; Polci, F; Renga, F; Voena, C; Ebert, M; Hartmann, T; Schröder, H; Waldi, R; Adye, T; Castelli, G; Franek, B; Olaiya, E O; Roethel, W; Wilson, F F; Emery, S; Escalier, M; Gaidot, A; Ganzhur, S F; Hamel de Monchenault, G; Kozanecki, W; Vasseur, G; Yèche, Ch; Zito, M; Chen, X R; Liu, H; Park, W; Purohit, M V; White, R M; Wilson, J R; Allen, M T; Aston, D; Bartoldus, R; Bechtle, P; Claus, R; Coleman, J P; Convery, M R; Dingfelder, J C; Dorfan, J; Dubois-Felsmann, G P; Dunwoodie, W; Field, R C; Glanzman, T; Gowdy, S J; 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; Luitz, S; Luth, V; Lynch, H L; Macfarlane, D B; Marsiske, H; Messner, R; Muller, D R; Nelson, S; O'Grady, C P; Ofte, I; Perazzo, A; Perl, M; Pulliam, T; 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; Wisniewski, W J; Wittgen, M; Wright, D H; Wulsin, H W; Yarritu, A K; Yi, K; Young, C C; Ziegler, V; Burchat, P R; Edwards, A J; Majewski, S A; Miyashita, T S; Petersen, B A; Wilden, L; Ahmed, S; Alam, M S; Bula, R; Ernst, J A; Pan, B; Saeed, M A; Zain, S B; Spanier, S M; Wogsland, B J; Eckmann, R; Ritchie, J L; Ruland, A M; Schilling, C J; Schwitters, R F; Izen, J M; Lou, X C; Ye, S; Bianchi, F; Gallo, F; Gamba, D; Pelliccioni, M; Bomben, M; Bosisio, L; Cartaro, C; Cossutti, F; 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; Hamano, K; Kowalewski, R; Nugent, I M; Roney, J M; Sobie, R J; Harrison, P F; Ilic, J; Latham, T E; Mohanty, G B; Band, H R; Chen, X; Dasu, S; Flood, K T; Hollar, J J; Kutter, P E; Pan, Y; Pierini, M; Prepost, R; Wu, S L; Neal, H

    2008-02-22

    A search for lepton flavor violating decays of a tau to a lighter-mass charged lepton and an omega vector meson is performed using 384.1 fb(-1) of e(+)e(-) annihilation data collected with the BABAR detector at the Stanford Linear Accelerator Center PEP-II storage ring. No signal is found, and the upper limits on the branching ratios are determined to be B(tau(+/-)-->e;{+/-}omega)<1.1 x10 (-7) and B(tau(+/-)-->micro(+/-)omega)<1.0 x 10(-7) at 90% confidence level. PMID:18352541

  2. Adaptive deployment of model reductions for tau-leaping simulation.

    PubMed

    Wu, Sheng; Fu, Jin; Petzold, Linda R

    2015-05-28

    Multiple time scales in cellular chemical reaction systems often render the tau-leaping algorithm inefficient. Various model reductions have been proposed to accelerate tau-leaping simulations. However, these are often identified and deployed manually, requiring expert knowledge. This is time-consuming and prone to error. In previous work, we proposed a methodology for automatic identification and validation of model reduction opportunities for tau-leaping simulation. Here, we show how the model reductions can be automatically and adaptively deployed during the time course of a simulation. For multiscale systems, this can result in substantial speedups.

  3. Caspase-Mediated Truncation of Tau Potentiates Aggregation

    PubMed Central

    Lee, Sangmook; Shea, Thomas B.

    2012-01-01

    Caspase-mediated truncation of tau is associated with aggregation. We examined the impact of manipulation of caspase activity on intracellular aggregation of a mutant form of tau (3PO) that forms spontaneous aggregates. Treatment with the caspase inhibitor Z-VAD-fmk reduced both N and C-terminal tau truncation but did not significantly reduce aggregation. Treatment with staurosporine, which activated caspases, increased C-terminal but not N-terminal truncation and enhanced aggregation. These findings suggest that caspase activation is one potential route, rather than an obligatory initiation step, in aggregation, and that N- and C-terminal truncation contribute differentially to aggregation. PMID:22988541

  4. Disentangling perturbative and power corrections in precision tau decay analysis

    SciTech Connect

    Gorbunov, D.S.; Pivovarov, A.A.

    2005-01-01

    Hadronic tau decay precision data are analyzed with account of both perturbative and power corrections of high orders within QCD. It is found that contributions of high order power corrections are essential for extracting a numerical value for the strange quark mass from the data on Cabibbo suppressed tau decays. We show that with inclusion of new five-loop perturbative corrections in the analysis the convergence of perturbation theory remains acceptable only for few low order moments. We obtain m{sub s}(M{sub {tau}})=130{+-}27 MeV in agreement with previous estimates.

  5. Extracellular Tau Paired Helical Filaments Differentially Affect Tau Pathogenic Mechanisms in Mitotic and Post-Mitotic Cells: Implications for Mechanisms of Tau Propagation in the Brain.

    PubMed

    Varghese, Merina; Santa-Maria, Ismael; Ho, Lap; Ward, Libby; Yemul, Shrishailam; Dubner, Lauren; Księżak-Reding, Hanna; Pasinetti, Giulio Maria

    2016-09-01

    The release of paired helical filaments (PHFs) from neurons into the extracellular space may contribute to the propagation of tau pathology across brain regions in Alzheimer's disease (AD) and other tauopathies. The majority of available mechanistic studies exploring the pathologic role of extracellular PHFs are conducted in proliferating cell lines. Here, we compare how extracellular PHFs induce tauopathy in mitotic cells and in post-mitotic brain neurons. In a mitotic cell line (HEK 293T), extracellular exposure to AD PHFs leads to an intracellular "aggresomal" type deposition of tau, coincidental with redistribution of dynein, a retrograde motor protein. We also observed that PHFs impaired proteasome degradation, but not autophagy. Exposure of cells to proteasome inhibitors was sufficient to induce intracellular tau aggregate formation as well as reorganization of dynein and the intermediate filament protein, vimentin. Thus, in mitotic cells, extracellular PHFs promote cellular tau aggregation, in part, by interfering with cellular proteasome degradation processes. In contrast with our observations with proliferating cells, exposure of post-mitotic primary neuronal cultures to AD PHFs did not promote "aggresomal" tau deposition, but instead resulted in a widespread accumulation of phosphorylated tau-immunoreactive swellings in neuritic processes, characterized by disturbed cytoskeletal organization of dynein and vimentin. Collectively, our observations suggest that extracellular PHFs may contribute to the propagation of tau pathology by independent mechanisms in post-mitotic and mitotic brain cells. These outcomes indicate that in addition to post-mitotic brain neurons, mitotic brain cells should also be considered as targets for therapeutic interventions to attenuate propagation of tauopathy.

  6. Conformation determines the seeding potencies of native and recombinant Tau aggregates.

    PubMed

    Falcon, Benjamin; Cavallini, Annalisa; Angers, Rachel; Glover, Sarah; Murray, Tracey K; Barnham, Luanda; Jackson, Samuel; O'Neill, Michael J; Isaacs, Adrian M; Hutton, Michael L; Szekeres, Philip G; Goedert, Michel; Bose, Suchira

    2015-01-01

    Intracellular Tau inclusions are a pathological hallmark of several neurodegenerative diseases, collectively known as the tauopathies. They include Alzheimer disease, tangle-only dementia, Pick disease, argyrophilic grain disease, chronic traumatic encephalopathy, progressive supranuclear palsy, and corticobasal degeneration. Tau pathology appears to spread through intercellular propagation, requiring the formation of assembled "prion-like" species. Several cell and animal models have been described that recapitulate aspects of this phenomenon. However, the molecular characteristics of seed-competent Tau remain unclear. Here, we have used a cell model to understand the relationships between Tau structure/phosphorylation and seeding by aggregated Tau species from the brains of mice transgenic for human mutant P301S Tau and full-length aggregated recombinant P301S Tau. Deletion of motifs (275)VQIINK(280) and (306)VQIVYK(311) abolished the seeding activity of recombinant full-length Tau, suggesting that its aggregation was necessary for seeding. We describe conformational differences between native and synthetic Tau aggregates that may account for the higher seeding activity of native assembled Tau. When added to aggregated Tau seeds from the brains of mice transgenic for P301S Tau, soluble recombinant Tau aggregated and acquired the molecular properties of aggregated Tau from transgenic mouse brain. We show that seeding is conferred by aggregated Tau that enters cells through macropinocytosis and seeds the assembly of endogenous Tau into filaments. PMID:25406315

  7. Acetylation of the KXGS motifs in tau is a critical determinant in modulation of tau aggregation and clearance

    PubMed Central

    Cook, Casey; Carlomagno, Yari; Gendron, Tania F.; Dunmore, Judy; Scheffel, Kristyn; Stetler, Caroline; Davis, Mary; Dickson, Dennis; Jarpe, Matthew; DeTure, Michael; Petrucelli, Leonard

    2014-01-01

    The accumulation of hyperphosphorylated tau in neurofibrillary tangles (NFTs) is a neuropathological hallmark of tauopathies, including Alzheimer's disease (AD) and chronic traumatic encephalopathy, but effective therapies directly targeting the tau protein are currently lacking. Herein, we describe a novel mechanism in which the acetylation of tau on KXGS motifs inhibits phosphorylation on this same motif, and also prevents tau aggregation. Using a site-specific antibody to detect acetylation of KXGS motifs, we demonstrate that these sites are hypoacetylated in patients with AD, as well as a mouse model of tauopathy, suggesting that loss of acetylation on KXGS motifs renders tau vulnerable to pathogenic insults. Furthermore, we identify histone deacetylase 6 (HDAC6) as the enzyme responsible for the deacetylation of these residues, and provide proof of concept that acute treatment with a selective and blood–brain barrier-permeable HDAC6 inhibitor enhances acetylation and decreases phosphorylation on tau's KXGS motifs in vivo. As such, we have uncovered a novel therapeutic pathway that can be manipulated to block the formation of pathogenic tau species in disease. PMID:23962722

  8. Multifrequency Study of Giant Radio Pulses from the Crab Pulsar with the K5 VLBI Recording Terminal

    NASA Astrophysics Data System (ADS)

    Popov, Mikhail; Soglasnov, Vladimir; Kondratiev, Vladislav; Bilous, Anna; Moshkina, Olga; Oreshko, Vasily; Ilyasov, Yury; Sekido, Mamoru; Kondo, Tetsuro

    2009-12-01

    Simultaneous multifrequency observations of Crab pulsar giant pulses (GPs) were performed with the 64-m Kalyazin radio telescope at four frequency (ν = 0.6, 1.4, 2.2, and 8.3 GHz) using the K5 VLBI recording terminal. The K5 terminal provided continuous recording in 16 × 4-MHz wide frequency channels distributed over 4 frequency bands. Several thousand GPs were detected during about 6 hours of observations on two successive days in 2005 July. The radio spectra of single GPs were analyzed at separate frequencies and over the whole frequency range. These spectra manifest notable modulation over the frequency ranges, Δν, both on large (Δν/ν ≈ 0.5) and small (Δν/ν ≈ 0.01) frequency scales. A cross-correlation analysis of GPs at 2.2 GHz showed that their pulse shapes can be interpreted as being an ensemble of unresolved bursts grouped together on time scales of ≈1μs, being well-correlated over a 60-MHz band. The corresponding GP cross-correlation functions do not obey the predictions of the amplitude-modulated noise model of Rickett(1975), thus indicating that unresolved components represent a small number of elementary emitters.

  9. The Impact of Grade Retention on K-5 Elementary Students: Perceptions of Educators in States Served by the Southern Association of Colleges and Schools.

    ERIC Educational Resources Information Center

    Patterson, Dolia McIntosh

    The purpose of this study was to analyze the perceptions of educators regarding the impact of grade retention on K-5 elementary students. Principals (N=384) and teachers (N=384) in K-5 elementary schools from 11 southern states were surveyed. The study included 169 responses from principals and 140 responses from teachers. The data revealed that…

  10. Exclusive Branching-Fraction Measurements of Semileptonic {tau} Decays into Three Charged Hadrons, into {phi}{pi}{sup -}{nu}{sub {tau}}, and into {phi}K{sup -}{nu}{sub {tau}}

    SciTech Connect

    Aubert, B.; Bona, M.; Boutigny, D.; Couderc, F.; Karyotakis, Y.; Lees, J. P.; Poireau, V.; Tisserand, V.; Zghiche, A.; Palano, A.; Chen, J. C.; Qi, N. D.; Rong, G.; Wang, P.; Zhu, Y. S.; Eigen, G.; Ofte, I.; Stugu, B.; Abrams, G. S.

    2008-01-11

    Using a data sample corresponding to an integrated luminosity of 342 fb{sup -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}{sup -}{yields}{pi}{sup -}{pi}{sup -}{pi}{sup +}{nu}{sub {tau}}(ex.K{sub S}{sup 0}))=(8.83{+-}0.01{+-}0.13)%, B({tau}{sup -}{yields}K{sup -}{pi}{sup -}{pi}{sup +}{nu}{sub {tau}}(ex.K{sub S}{sup 0}))=(0.273{+-}0.002{+-}0.009)%, B({tau}{sup -}{yields}K{sup -}{pi}{sup -}K{sup +}{nu}{sub {tau}})=(0.1346{+-}0.0010{+-}0.0036)%, and B({tau}{sup -}{yields}K{sup -}K{sup -}K{sup +}{nu}{sub {tau}})=(1.58{+-}0.13{+-}0.12)x10{sup -5}, where the uncertainties are statistical and systematic, respectively. These include significant improvements over previous measurements and a first measurement of B({tau}{sup -}{yields}K{sup -}K{sup -}K{sup +}{nu}{sub {tau}}) in which no resonance structure is assumed. We also report a first measurement of B({tau}{sup -}{yields}{phi}{pi}{sup -}{nu}{sub {tau}})=(3.42{+-}0.55{+-}0.25)x10{sup -5}, a new measurement of B({tau}{sup -}{yields}{phi}K{sup -}{nu}{sub {tau}})=(3.39{+-}0.20{+-}0.28)x10{sup -5} and a first upper limit on B({tau}{sup -}{yields}K{sup -}K{sup -}K{sup +}{nu}{sub {tau}}(ex.{phi}))

  11. Pattern of tau hyperphosphorylation and neurotransmitter markers in the brainstem of senescent tau filament forming transgenic mice.

    PubMed

    Morcinek, Kerstin; Köhler, Christoph; Götz, Jürgen; Schröder, Hannsjörg

    2013-02-25

    The early occurrence of brainstem-related symptoms, e.g. gait and balance impairment, apathy and depression in Alzheimer's disease patients suggests brainstem involvement in the initial pathogenesis. To address the question whether tau filament forming mice expressing mutated human tau mirror histopathological changes observed in Alzheimer brainstem, the degree and distribution of neurofibrillary lesions as well as the pattern of cholinergic and monoaminergic neurons were investigated. The expression of the human tau transgene was observed in multiple brainstem nuclei, particularly in the magnocellular reticular formation, vestibular nuclei, cranial nerve motor nuclei, sensory trigeminal nerve nuclei, inferior and superior colliculi, periaqueductal and pontine gray matter, and the red nucleus. Most of the human tau-immunoreactive cell groups also showed tau hyperphosphorylation at the epitopes Thr231/Ser235 and Ser202/Thr205, while abnormal tau phosphorylation at the epitope Ser422 or silver stained structures were almost totally lacking. We found no obvious differences in distribution and density of cholinergic and monoaminergic neurons between tau-transgenic and wild type mice. Although numerous brainstem nuclei in our model expressed human tau protein, the development of neurofibrillary tangles, neuropil threads and ghost tangles was rare and likewise its distribution differed largely from Alzheimer's disease pattern. The number of monoaminergic neurons remained unchanged in the transgenic mice, while monoaminergic nuclei in Alzheimer brainstem showed a distinct neuronal loss. However, the distribution of pretangle-affected neurons in the tau-transgenic mice partly resembled those seen in progressive supranuclear palsy, presenting these animals as a model to examine brainstem pathogenesis of progressive supranuclear palsy. PMID:23261664

  12. Study of High-multiplicity 3-prong and 5-prong Tau Decays at BaBar

    SciTech Connect

    Lees, J.P

    2012-06-01

    We present measurements of the branching fractions of 3-prong and 5-prong {tau} decay modes using a sample of 430 million {tau} lepton pairs, corresponding to an integrated luminosity of 468 fb{sup -1}, collected with the BABAR detector at the PEP-II asymmetric energy e{sup +}e{sup -} storage rings. The {tau}{sup -} {yields} (3{pi}){sup -} {eta}{nu}{sub {tau}}, {tau}{sup -} {yields} (3{pi}){sup -} {yields} {omega}{nu}{sub {tau}} and {tau}{sup -} {yields} {pi}{sup -} f{sub 1}(1285){nu}{sub {tau}} branching fractions are presented as well as a new limit on the branching fraction of the isospin-forbidden, second-class current {tau}{sup -} {yields} {pi}{sup -} {eta}{prime}(958){nu}{sub {tau}} decay. We find no evidence for charged kaons in these decay modes and place the first upper limits on their branching fractions.

  13. The neuritic plaque facilitates pathological conversion of tau in an Alzheimer's disease mouse model

    PubMed Central

    Li, Tong; Braunstein, Kerstin E.; Zhang, Juhong; Lau, Ashley; Sibener, Leslie; Deeble, Christopher; Wong, Philip C.

    2016-01-01

    A central question in Alzheimer's Disease (AD) is whether the neuritic plaque is necessary and sufficient for the development of tau pathology. Hyperphosphorylation of tau is found within dystrophic neurites surrounding β-amyloid deposits in AD mouse models but the pathological conversion of tau is absent. Likewise, expression of a human tau repeat domain in mice is insufficient to drive the pathological conversion of tau. Here we developed an Aβ-amyloidosis mouse model that expresses the human tau repeat domain and show that in these mice, the neuritic plaque facilitates the pathological conversion of wild-type tau. We show that this tau fragment seeds the neuritic plaque-dependent pathological conversion of wild-type tau that spreads from the cortex and hippocampus to the brain stem. These results establish that in addition to the neuritic plaque, a second determinant is required to drive the conversion of wild-type tau. PMID:27373369

  14. Search for CP Violation in the Decay tau- \\to pi- K^0_S (>= 0 pi0) nu_tau

    SciTech Connect

    Lees, J.P.; Poireau, V.; Tisserand, V.; Garra Tico, J.; Grauges, E.; Martinelli, M.; Milanes, D.A.; Palano, A.; Pappagallo, M.; Eigen, G.; Stugu, B.; Brown, D.N.; Kerth, L.T.; Kolomensky, Yu.G.; Lynch, G.; Koch, H.; Schroeder, T.; Asgeirsson, D.J.; Hearty, C.; Mattison, T.S.; McKenna, J.A.; /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 /INFN, Ferrara /Ferrara U. /INFN, Ferrara /Frascati /INFN, Genoa /Genoa U. /INFN, Genoa /INFN, Genoa /Genoa U. /INFN, Genoa /Indian Inst. Tech., Guwahati /Harvard U. /Harvey Mudd Coll. /Heidelberg U. /Humboldt U., Berlin /Imperial Coll., London /Iowa State U. /Iowa State U. /Johns Hopkins U. /Paris U., VI-VII /LLNL, Livermore /Liverpool U. /Queen Mary, U. of London /Royal Holloway, 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 /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. /Pisa U. /Pisa, Scuola Normale Superiore /INFN, Pisa /Pisa U. /INFN, Pisa /INFN, Pisa /Pisa U. /INFN, Pisa /Princeton U. /INFN, Rome /INFN, Rome /Rome U. /INFN, Rome /INFN, Rome /Rome U. /INFN, Rome /Rostock U. /Rutherford /DAPNIA, Saclay /SLAC /South Carolina U. /Southern Methodist U. /Stanford U., Phys. Dept. /SUNY, Albany /Tel Aviv U. /Tennessee U. /Texas Nuclear Corp., Austin /Texas U., Dallas /INFN, Turin /Turin U. /INFN, Trieste /Trieste U. /Valencia U. /Victoria U. /Warwick U. /Wisconsin U., Madison

    2012-02-16

    We report a search for CP violation in the decay {tau}{sup -} {yields} {pi}{sup -}K{sub S}{sup 0}({>=} 0{pi}{sup 0}){nu}{sub {tau}} using a dataset of 437 million {tau} lepton pairs, corresponding to an integrated luminosity of 476 fb{sup -1}, collected with the BABAR detector at the PEP-II asymmetric energy e{sup +}e{sup -} storage rings. The CP-violating decay-rate asymmetry is determined to be (-0.45 {+-} 0.24 {+-} 0.11)%, approximately three standard deviations from the Standard Model prediction of (0.33 {+-} 0.01)%.

  15. Structure and mechanism of action of tau aggregation inhibitors

    PubMed Central

    Cisek, Katryna; Cooper, Grace L.; Huseby, Carol J.; Kuret, Jeff

    2015-01-01

    Since the discovery of phenothiazines as tau protein aggregation inhibitors, many additional small molecule inhibitors of diverse chemotype have been discovered and characterized in biological model systems. Although direct inhibition of tau aggregation has shown promise as a potential treatment strategy for depressing neurofibrillary lesion formation in Alzheimer’s disease, the mechanism of action of these compounds has been unclear. However, recent studies have found that tau aggregation antagonists exert their effects through both covalent and non-covalent means, and have identified associated potency and selectivity driving features. Here we review small-molecule tau aggregation inhibitors with a focus on compound structure and inhibitory mechanism. The elucidation of inhibitory mechanism has implications for maximizing on-target efficacy while minimizing off-target side effects. PMID:25387336

  16. Tau protein role in sleep-wake cycle.

    PubMed

    Cantero, Jose L; Hita-Yañez, Eva; Moreno-Lopez, Bernardo; Portillo, Federico; Rubio, Alicia; Avila, Jesus

    2010-01-01

    Evidence has shown that the lack of tau produces subtle changes in neuronal structure and modest impairment in complex behaviors, suggesting compensatory mechanisms carried out by other neuronal microtubule-associated proteins. Here we show major abnormalities in sleep-wake cycle of tau-deficient animals including increased wakefulness duration and decreased non-rapid eye movement (NREM) sleep time, a higher number of state transitions between NREM and wake, and shortened sleep bouts. Altered sleep structure in tau-/- mice was accompanied by a significant decline in delta power together with an enhanced spectral density of sleep spindles during NREM sleep. No significant differences were observed in rapid eye movement (REM) sleep between the two mouse strains. Taken together, these results suggest that tau indirectly participates in the regulation of the sleep-wake cycle modulating not only the control and maintenance of global brain states but also the cerebral oscillatory patterns underlying sleep-wake states.

  17. Tau/Amyloid Beta 42 Peptide Test (Alzheimer Biomarkers)

    MedlinePlus

    ... page: Was this page helpful? Also known as: Alzheimer Biomarkers Formal name: Tau Protein and Amyloid Beta ... supplemental tests to help establish a diagnosis of Alzheimer disease and to distinguish between AD and other ...

  18. Tau as a Therapeutic Target for Alzheimer’s Disease

    PubMed Central

    Boutajangout, Allal; Sigurdsson, Einar M.; Krishnamurthy, Pavan K.

    2012-01-01

    Neurofibrillary tangles (NFTs) are one of the pathological hallmarks of Alzheimer’s disease (AD) and are primarily composed of aggregates of hyperphosphorylated forms of the microtubule associated protein tau. It is likely that an imbalance of kinase and phosphatase activities leads to the abnormal phosphorylation of tau and subsequent aggregation. The wide ranging therapeutic approaches that are being developed include to inhibit tau kinases, to enhance phosphatase activity, to promote microtubule stability, and to reduce tau aggregate formation and/or enhance their clearance with small molecule drugs or by immunotherapeutic means. Most of these promising approaches are still in preclinical development whilst some have progressed to Phase II clinical trials. By pursuing these lines of study, a viable therapy for AD and related tauopathies may be obtained. PMID:21679154

  19. Loss of tau rescues inflammation-mediated neurodegeneration

    PubMed Central

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

    2015-01-01

    Neuroinflammation is one of the neuropathological hallmarks of Alzheimer's disease (AD) and related tauopathies. Activated microglia spatially coexist with microtubule-associated protein tau (Mapt or tau)-burdened neurons in the brains of human AD and non-AD tauopathies. Numerous studies have suggested that neuroinflammation precedes tau pathology and that induction or blockage of neuroinflammation via lipopolysaccharide (LPS) or anti-inflammatory compounds (such as FK506) accelerate or block tau pathology, respectively in several animal models of tauopathy. We have previously demonstrated that microglia-mediated neuroinflammation via deficiency of the microglia-specific chemokine (fractalkine) receptor, CX3CR1, promotes tau pathology and neurodegeneration in a mouse model of LPS-induced systemic inflammation. Here, we demonstrate that tau mediates the neurotoxic effects of LPS in Cx3cr1−/− mice. First, Mapt+/+ neurons displayed elevated levels of Annexin V (A5) and TUNEL (markers of neurodegeneration) when co-cultured with LPS-treated Cx3cr1−/−microglia, which is rescued in Mapt−/− neurons. Second, a neuronal population positive for phospho-S199 (AT8) tau in the dentate gyrus is also positive for activated or cleaved caspase (CC3) in the LPS-treated Cx3cr1−/− mice. Third, genetic deficiency for tau in Cx3cr1−/− mice resulted in reduced microglial activation, altered expression of inflammatory genes and a significant reduction in the number of neurons positive for CC3 compared to Cx3cr1−/−mice. Finally, Cx3cr1−/−mice exposed to LPS displayed a lack of inhibition in an open field exploratory behavioral test, which is rescued by tau deficiency. Taken together, our results suggest that pathological alterations in tau mediate inflammation-induced neurotoxicity and that deficiency of Mapt is neuroprotective. Thus, therapeutic approaches toward either reducing tau levels or blocking neuroinflammatory pathways may serve as a potential strategy

  20. Lepton-Flavor-Violating Tau Decays at BaBar

    SciTech Connect

    Marchiori, G.; /Paris, LPTHE

    2012-04-09

    We present the most recent searches for lepton-flavor-violating (LFV) {tau} decays in BABAR. We find no evidence of {tau} decaying to three charged leptons or to a charged lepton and a neutral meson (K{sub S}{sup 0}, {rho}, {phi}, K*{sup 0}, {bar K}*{sup 0}), and set upper limits on the corresponding branching fractions (BF) between 1.8 and 19 x 10{sup -8} at 90% confidence level (CL).

  1. Lepton Flavour Violation in Tau Decays at BaBar

    SciTech Connect

    Wilson, F.F.; /Rutherford

    2011-11-07

    Recent results from {tau} physics studies at BABAR are presented with an emphasis on Lepton Flavour Violation measurements. The results from the current generation of B-meson Factories are already beginning to constrain the parameter space of models that go beyond the Standard Model. By the end of their data-taking, the current generation of B-meson factories will have produced nearly 2 billion {tau} pair decays. The physics potential of this legacy has only just begun to be exploited.

  2. Physics of a high-luminosity Tau-Charm Factory

    SciTech Connect

    King, M.E.

    1992-10-01

    This paper highlights the physics capabilities of a Tau-Charm Factory; i.e., high luminosity ({approximately}10{sup 33}cm{sup {minus}2}s{sup {minus}1}) e{sup +}e{sup {minus}} collider operating in the center-of-mass energy range of 3-5 GeV, with a high-precision, general-purpose detector. Recent developments in {tau} and charm physics are emphasized.

  3. Experimental upper limits on branching fractions for unexpected decay modes of the tau lepton

    SciTech Connect

    Hayes, K.G.; Perl, M.L.; Alam, M.S.; Boyarski, A.M.; Breidenbach, M.; Burke, D.L.; Dorenbosch, J.; Dorfan, J.M.; Feldman, G.J.; Franklin, M.E.B.; Hanson, G.; Himel, T.; Hitlin, D.G.; Hollebeek, R.J.; Innes, W.R.; Jaros, J.A.; Jenni, P.; Larsen, R.R.; Lueth, V.; Richter, B.; Roussarie, A.; Scharre, D.L.; Schindler, R.H.; Schwitters, R.F.; Siegrist, J.L.; Taureg, H.; Tonutti, M.; Vidal, R.A.; Weiss, J.M.; Zaccone, H.; Abrams, G.S.; Blocker, C.A.; Blondel, A.; Carithers, W.C.; Chinowsky, W.; Coles, M.W.; Cooper, S.; Dieterle, W.E.; Dillon, J.B.; Eaton, M.W.; Gidal, G.; Goldhaber, G.; Johnson, A.D.; Kadyk, J.A.; Lankford, A.J.; Levi, M.; Millikan, R.E.; Nelson, M.E.; Pang, C.Y.; Patrick, J.F.; Strait, J.; Trilling, G.H.; Vella, E.N.; Videau, I.

    1982-06-01

    Searches for 12 neutrinoless decay modes of the tau which violate lepton-number conservation have been made using the reaction e/sup +/e/sup -/..-->..tau/sup +/tau/sup -/. No evidence for lepton-number violation is observed, and we have set upper limits (90% C.L.) on the branching ratio for each decay mode. The branching-ratio limits on the radiative decays tau..--> mu gamma.. and tau..-->..e..gamma.. are 0.055 and 0.064, respectively. For the charged lepton decays tau..-->..eee, tau..-->..e..mu mu.., tau..--> mu..ee, and tau..--> mu mu mu.., the branching ratio limits are 0.040, 0.033, 0.044, and 0.049%, respectively. Upper limits on the branching ratios for the following charged lepton-neutral hadron decays are: tau..-->..erho/sup 0/ (0.037%), tau..--> mu..rho/sup 0/ (0.044%), tau..-->..eK/sup 0/ (0.13%), tau..--> mu..K/sup 0/ (0.10%), tau..-->..e..pi../sup 0/ (0.21%), and tau..--> mu pi../sup 0/ (0.082%). We also use these data to search for the pair production in e/sup +/e/sup -/ annihilation of some unconventional particles with masses less than about 3 GeV/c/sup 2/.

  4. SUMOylation at K340 inhibits tau degradation through deregulating its phosphorylation and ubiquitination

    PubMed Central

    Luo, Hong-Bin; Xia, Yi-Yuan; Shu, Xi-Ji; Liu, Zan-Chao; Feng, Ye; Liu, Xing-Hua; Yu, Guang; Yin, Gang; Xiong, Yan-Si; Zeng, Kuan; Jiang, Jun; Ye, Keqiang; Wang, Xiao-Chuan; Wang, Jian-Zhi

    2014-01-01

    Intracellular accumulation of the abnormally modified tau is hallmark pathology of Alzheimer’s disease (AD), but the mechanism leading to tau aggregation is not fully characterized. Here, we studied the effects of tau SUMOylation on its phosphorylation, ubiquitination, and degradation. We show that tau SUMOylation induces tau hyperphosphorylation at multiple AD-associated sites, whereas site-specific mutagenesis of tau at K340R (the SUMOylation site) or simultaneous inhibition of tau SUMOylation by ginkgolic acid abolishes the effect of small ubiquitin-like modifier protein 1 (SUMO-1). Conversely, tau hyperphosphorylation promotes its SUMOylation; the latter in turn inhibits tau degradation with reduction of solubility and ubiquitination of tau proteins. Furthermore, the enhanced SUMO-immunoreactivity, costained with the hyperphosphorylated tau, is detected in cerebral cortex of the AD brains, and β-amyloid exposure of rat primary hippocampal neurons induces a dose-dependent SUMOylation of the hyperphosphorylated tau. Our findings suggest that tau SUMOylation reciprocally stimulates its phosphorylation and inhibits the ubiquitination-mediated tau degradation, which provides a new insight into the AD-like tau accumulation. PMID:25378699

  5. Potent inhibition of tau fibrillization with a multivalent ligand

    SciTech Connect

    Honson, Nicolette S.; Jensen, Jordan R.; Darby, Michael V.; Kuret, Jeff

    2007-11-09

    Small-molecule inhibitors of tau fibrillization are under investigation as tools for interrogating the tau aggregation pathway and as potential therapeutic agents for Alzheimer's disease. Established inhibitors include thiacarbocyanine dyes, which can inhibit recombinant tau fibrillization in the presence of anionic surfactant aggregation inducers. In an effort to increase inhibitory potency, a cyclic bis-thiacarbocyanine molecule containing two thiacarbocyanine moieties was synthesized and characterized with respect to tau fibrillization inhibitory activity by electron microscopy and ligand aggregation state by absorbance spectroscopy. Results showed that the inhibitory activity of the bis-thiacarbocyanine was qualitatively similar to a monomeric cyanine dye, but was more potent with 50% inhibition achieved at {approx}80 nM concentration. At all concentrations tested in aqueous solution, the bis-thiacarbocyanine collapsed to form a closed clamshell structure. However, the presence of tau protein selectively stabilized the open conformation. These results suggest that the inhibitory activity of bis-thiacarbocyanine results from multivalency, and reveal a route to more potent tau aggregation inhibitors.

  6. The Triple Binary Star EQ Tau with an Active Component

    NASA Astrophysics Data System (ADS)

    Li, K.; Qian, S.-B.; Hu, S.-M.; He, J.-J.

    2014-05-01

    New photometric data of EQ Tau observed in 2010 and 2013 are presented. Light curves obtained in 2000 and 2004 by Yuan & Qian and 2001 by Yang & Liu, together with our two newly determined sets of light curves, were analyzed using the Wilson-Devinney code. The five sets of light curves exhibit very obvious variations, implying that the light curves of EQ Tau show a strong O'Connell effect. We found that EQ Tau is an A-type shallow contact binary with a contact degree of f = 11.8%; variable dark spots on the primary component of EQ Tau were also observed. Using 10 new times of minimum light, together with those collected from the literature, the orbital period change of EQ Tau was analyzed. We found that its orbital period includes a secular decrease (dP/dt = -3.63 × 10-8 days yr-1) and a cyclic oscillation (A 3 = 0.0058 days and P 3 = 22.7 yr). The secular increase of the period can be explained by mass transfer from the more massive component to the less massive one or/and angular momentum loss due to a magnetic stellar wind. The Applegate mechanism cannot explain the cyclic orbital period change. A probable transit-like event was observed in 2010. Therefore, the cyclic orbital period change of EQ Tau may be due to the light time effect of a third body.

  7. The triple binary star EQ Tau with an active component

    SciTech Connect

    Li, K.; Hu, S.-M.; Qian, S.-B.; He, J.-J. E-mail: likai@ynao.ac.cn

    2014-05-01

    New photometric data of EQ Tau observed in 2010 and 2013 are presented. Light curves obtained in 2000 and 2004 by Yuan and Qian and 2001 by Yang and Liu, together with our two newly determined sets of light curves, were analyzed using the Wilson-Devinney code. The five sets of light curves exhibit very obvious variations, implying that the light curves of EQ Tau show a strong O'Connell effect. We found that EQ Tau is an A-type shallow contact binary with a contact degree of f = 11.8%; variable dark spots on the primary component of EQ Tau were also observed. Using 10 new times of minimum light, together with those collected from the literature, the orbital period change of EQ Tau was analyzed. We found that its orbital period includes a secular decrease (dP/dt = –3.63 × 10{sup –8} days yr{sup –1}) and a cyclic oscillation (A {sub 3} = 0.0058 days and P {sub 3} = 22.7 yr). The secular increase of the period can be explained by mass transfer from the more massive component to the less massive one or/and angular momentum loss due to a magnetic stellar wind. The Applegate mechanism cannot explain the cyclic orbital period change. A probable transit-like event was observed in 2010. Therefore, the cyclic orbital period change of EQ Tau may be due to the light time effect of a third body.

  8. Identification of an aggregation-prone structure of tau

    PubMed Central

    Elbaum-Garfinkle, Shana; Rhoades, Elizabeth

    2012-01-01

    The aggregation and deposition of normally soluble proteins is the hallmark of several devastating neurodegenerative disorders. For proteins such as tau in Alzheimer’s disease and α-synuclein in Parkinson’s disease, aggregation involves a transition from an intrinsically disordered monomer to a highly structured fiber. While understanding the role of these proteins in neurodegeneration requires elucidation of the structural basis of self-association, the conformational heterogeneity of disordered proteins makes their structural characterization inherently challenging. Here we use single molecule Förster resonance energy transfer to measure the conformational ensemble of tau in the absence and presence of heparin to identify critical conformational changes relevant to the initiation of aggregation. We find that different domains of tau display distinct conformational properties that are strongly correlated with their degree of disorder and which may relate to their roles in aggregation. Moreover, we observe that heparin binding induces a distinct two-state structural transition in tau described by a loss of long-range contacts and a concomitant compaction of the microtubule binding domain. Our results describe a conformational intermediate of tau that precedes the formation of aggregates and could serve as a target for tau-focused therapeutics. PMID:22998648

  9. A measurement of the tau Michel parameters at SLD

    SciTech Connect

    Quigley, J.

    1997-05-01

    This thesis presents a measurement of the tau Michel parameters. This measurement utilizes the highly polarized SLC electron beam to extract these quantities directly from the measured tau decay spectra using the 1993--95 SLD sample of 4,528 tau pair events. The results are {rho}{sup e} = 0.71 {+-} 0.14 {+-} 0.05, {xi}{sup e} = 1.16 {+-} 0.52 {+-} 0.06, and ({xi}{delta}){sup e} = 0.85 {+-} 0.43 {+-} 0.08 for tau decays to electrons and {rho}{sup {mu}} = 0.54 {+-} 0.28 {sup {minus}} 0.14, {eta}{sup {mu}} = {minus}0.59 {+-} 0.82 {+-} 0.45, {xi}{sup {mu}} = 0.75 {+-} 0.50 {+-} 0.14, and ({xi}{delta}){sup {mu}} = 0.82 {+-} 0.32 {+-} 0.07 for tau decays to muons. Combining all leptonic tau decays gives {rho} = 0.72 {+-} 0.09 {+-} 0.03, {xi} = 1.05 {+-} 0.35 {+-} 0.04, and {Xi}{delta} = 0.88 {+-} 0.27 {+-} 0.04. These results agree well with the current world average and the Standard Model.

  10. Dietary docosahexaenoic acid and docosapentaenoic acid ameliorate amyloid-beta and tau pathology via a mechanism involving presenilin 1 levels.

    PubMed

    Green, Kim N; Martinez-Coria, Hilda; Khashwji, Hasan; Hall, Eileen B; Yurko-Mauro, Karin A; Ellis, Lorie; LaFerla, Frank M

    2007-04-18

    The underlying cause of sporadic Alzheimer disease (AD) is unknown, but a number of environmental and genetic factors are likely to be involved. One environmental factor that is increasingly being recognized as contributing to brain aging is diet, which has evolved markedly over modern history. Here we show that dietary supplementation with docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid, in the 3xTg-AD mouse model of AD reduced the intraneuronal accumulation of both amyloid-beta (Abeta) and tau. In contrast, combining DHA with n-6 fatty acids, either arachidonic acid or docosapentaenoic acid (DPAn-6), diminished the efficacy of DHA over a 12 month period. Here we report the novel finding that the mechanism accounting for the reduction in soluble Abeta was attributable to a decrease in steady-state levels of presenilin 1, and not to altered processing of the amyloid precursor protein by either the alpha- or beta-secretase. Furthermore, the presence of DPAn-6 in the diet reduced levels of early-stage phospho-tau epitopes, which correlated with a reduction in phosphorylated c-Jun N-terminal kinase, a putative tau kinase. Collectively, these results suggest that DHA and DPAn-6 supplementations could be a beneficial natural therapy for AD.

  11. Alpha-1 Antitrypsin Deficiency

    MedlinePlus

    ... from the NHLBI on Twitter. What Is Alpha-1 Antitrypsin Deficiency? Alpha-1 antitrypsin (an-tee-TRIP-sin) deficiency, or AAT ... as it relates to lung disease. Overview Alpha-1 antitrypsin, also called AAT, is a protein made ...

  12. Preliminary Measurement of B(tau- ---> K- pi0 nu/tau) Using the BaBar Detector

    SciTech Connect

    Salvatore, F.; Lyon, A.J.; /Manchester U.

    2005-07-08

    A preliminary measurement of the branching fraction {Beta}({tau}{sup -} {yields} K{sup -}{pi}{sup 0}{nu}{sub {tau}}) is made using 124.4 fb{sup -1} of e{sup +}e{sup -} collision data provided by the PEP-II accelerator, operating primarily at {radical}s = 10.58 GeV, and recorded using the BABAR detector. They measure: {Beta}({tau}{sup -} {yields} K{sup -} {pi}{sup 0}{nu}{sub {tau}}) = (0.438 {+-} 0.004(stat) {+-} 0.022(syst))%. This result is the world's most precise measurement of this branching fraction to date and is consistent with the world average.

  13. Electroweak effects in e/sup +/e/sup -/. -->. tau/sup +/tau/sup -/ at 29 GeV

    SciTech Connect

    Fernandez, E.; Ford, W.T.; Qi, N.; Read A.L. Jr.; Smith, J.G.; Camporesi, T.; De Sangro, R.; Marini, A.; Peruzzi, I.; Piccolo, M.; Ronga, F.; Blume, H.T.; Hurst, R.B.; Venuti, J.P.; Wald, H.B.; Weinstein, R.; Band, H.R.; Gettner, M.W.; Goderre, G.P.; Meyer, O.A.; Moromisato, J.H.; Shambroom, W.D.; Sleeman, J.C.; von Goeler, E.; Ash, W.W.; Chadwick, G.B.; Clearwater, S.H.; Coombes, R.W.; Kaye, H.S.; Lau, K.H.; Leedy, R.E.; Lynch, H.L.; Messner, R.L.; Moss, L.J.; Muller, F.; Nelson, H.N.; Ritson, D.M.; Rosenberg, L.J.; Wiser, D.E.; Zdarko, R.W.; Groom, D.E.; Lee, H.; Delfino, M.C.; Heltsley, B.K.; Johnson, J.R.; Lavine, T.L.; Maruyama, T.; Prepost, R.

    1985-04-15

    A high-statistics measurement is presented of the cross section for the process e/sup +/e/sup -/..-->..tau/sup +/tau/sup -/ at ..sqrt..s = 29 GeV from the MAC detector at PEP. A fit to the angular distribution of our sample of 10 153 events with Vertical BarcosthetaVertical Bar<0.9 gives an asymmetry A/sub tautau/ = -0.055 +- 0.012 +- 0.005 from which we find the product of electron and tau axial-vector weak neutral couplings g/sub A//sup e/G/sub A//sup tau/ = 0.22 +- 0.05.

  14. Evidence for B+ {yields} {tau}+{nu}{tau} decays and measurement of fB from Belle

    SciTech Connect

    Kwon, Youngjoon

    2007-02-27

    We present the first evidence for B+ {yields} {tau}+{nu}{tau} decay, using 414 fb-1 of B meson decay event sample collected with the Belle detector at the KEKB e+e- collider. To cope with large missing energy due to multiple neutrinos in the final state, events are tagged by fully reconstructing one of the B mesons. We find the evidence for signal with a significance of 3.5 {sigma} including systematic uncertainties. The branching fraction is measured to be B(B{sup +} {yields} {tau}{sup +}{nu}{sub {tau}}) (1.79{sub -0.49-0.51}{sup +0.56+0.46}) x 10{sup -4}. From this we obtain f{sub B} = 0.229{sub -0.031-0.037}{sup +0.036+0.034} GeV, the first direct determination of the B meson decay constant.

  15. ATLAS Search for SM H{yields}{tau}{tau} in the VBF Production Mode

    SciTech Connect

    Hanninger, Guilherme Nunes

    2008-11-23

    This article discusses the search for the Standard Model Higgs boson produced in vector boson fusion and subsequent decay into {tau} pairs with the ATLAS detector at the Large Hadron Collider. This analysis is based on Monte Carlo signal and background samples simulated with a detailed detector description and the entire trigger chain. Preliminary results are reported including the expected discovery potential with 30 fb{sup -1} of data as well as the 95% expected signal exclusion with 10 fb{sup -1}.

  16. Crystal structures of the glutamate receptor ion channel GluK3 and GluK5 amino terminal domains

    PubMed Central

    Kumar, Janesh; Mayer, Mark L.

    2010-01-01

    Ionotropic glutamate receptors (iGluRs) mediate the majority of fast excitatory synaptic neurotransmission in the central nervous system. The selective assembly of iGluRs into the AMPA, kainate and NMDA receptor subtypes is regulated by their extracellular amino terminal domains (ATD). Kainate receptors are further classified into low-affinity (GluK1-3) and high-affinity (GluK4-5) receptor families based on their affinity for the neurotoxin kainic acid. These two families share 42% sequence identity for the intact receptor but only 28% sequence identity at the level of ATD. We have determined for the first time high-resolution crystal structures for the GluK3 and GluK5 ATDs, both of which crystallize as dimers, but with a strikingly different dimer assembly at the R1 interface. By contrast, for both GluK3 and GluK5 the R2 domain dimer assembly is similar to that reported previously for other non-NMDA iGluRs. This observation is consistent with the reports that GluK4-5 cannot form functional homomeric ion channels and require obligate coassembly with GluK1-3. Our analysis also reveals that the relative orientation of domains R1 and R2 in individual non-NMDA receptor ATDs varies by up to 10°, in contrast to the 50° difference reported for the NMDA receptor GluN2B subunit. This restricted domain movement in non-NMDA receptor ATDs seems to result from both extensive intramolecular contacts between domains R1 and R2, and from their assembly as dimers which interact at both the R1 and R2 domains. Our results provide the first insights into the structure and function for GluK4-5, the least understood family of iGluRs. PMID:20951142

  17. Enhanced tau neutrino appearance through invisible decay

    NASA Astrophysics Data System (ADS)

    Pagliaroli, Giulia; Di Marco, Natalia; Mannarelli, Massimo

    2016-06-01

    The decay of neutrino mass eigenstates leads to a change of the conversion and survival probability of neutrino flavor eigenstates. Exploiting the recent results released by the long-baseline OPERA experiment we perform the statistical investigation of the neutrino invisible decay hypothesis in the νμ→ντ appearance channel. We find that the neutrino decay provides an enhancement of the expected tau appearance signal with respect to the standard oscillation scenario for the long-baseline OPERA experiment. The increase of the νμ→ντ conversion probability by the decay of one of the mass eigenstates is due to a reduction of the "destructive interference" among the different massive neutrino components. Despite data showing a very mild preference for invisible decays with respect to the oscillations only hypothesis, we provide an upper limit for the neutrino decay lifetime in this channel of τ3/m3≳1.3 ×10-13 s /eV at the 90% confidence level.

  18. Tau Pathology Spread in PS19 Tau Transgenic Mice Following Locus Coeruleus (LC) Injections of Synthetic Tau Fibrils is Determined by the LC’s Afferent and Efferent Connections

    PubMed Central

    Iba, Michiyo; McBride, Jennifer D.; Guo, Jing L.; Zhang, Bin; Trojanowski, John Q.; Lee, Virginia M.-Y.

    2015-01-01

    Filamentous tau inclusions are hallmarks of Alzheimer’s disease (AD) and other neurodegenerative tauopathies. An increasing number of studies implicate the cell-to-cell propagation of tau pathology in the progression of tauopathies. We recently showed [25] that inoculation of preformed synthetic tau fibrils (tau PFFs) into the hippocampus of young transgenic (Tg) mice (PS19) overexpressing human P301S mutant tau induced robust tau pathology in anatomically connected brain regions including the locus coeruleus (LC). Since Braak and colleagues hypothesized that the LC is the first brain structure to develop tau lesions and since LC has widespread connections throughout the CNS, LC neurons could be the critical initiators of the stereotypical spreading of tau pathology through connectome-dependent transmission of pathological tau in AD. Here, we report that injections of tau PFFs into the LC of PS19 mice induced propagation of tau pathology to major afferents and efferents of the LC. Notably, tau pathology propagated along LC efferent projections was localized not only to axon terminals but also to neuronal perikarya, suggesting transneuronal transfer of templated tau pathology to neurons receiving LC projections. Further, brainstem neurons giving rise to major LC afferents also developed perikaryal tau pathology. Surprisingly, while tangle bearing neurons degenerated in the LC ipsilateral to the injection site starting 6 months post-injection, no neuron loss was seen in the contralateral LC wherein tangle bearing neurons gradually cleared tau pathology by 6–12 months post-injection. However, the spreading pattern of tau pathology observed in our LC-injected mice is different from that in AD brains since hippocampus and entorhinal cortex, which are affected in early stages of AD, were largely spared of tau inclusions in our model. Thus, while our study tested critical aspects of the Braak hypothesis of tau pathology spread, this novel mouse model provides unique

  19. High-Molecular-Weight Paired Helical Filaments from Alzheimer Brain Induces Seeding of Wild-Type Mouse Tau into an Argyrophilic 4R Tau Pathology in Vivo.

    PubMed

    Audouard, Emilie; Houben, Sarah; Masaracchia, Caterina; Yilmaz, Zehra; Suain, Valérie; Authelet, Michèle; De Decker, Robert; Buée, Luc; Boom, Alain; Leroy, Karelle; Ando, Kunie; Brion, Jean-Pierre

    2016-10-01

    In Alzheimer disease, the development of tau pathology follows neuroanatomically connected pathways, suggesting that abnormal tau species might recruit normal tau by passage from cell to cell. Herein, we analyzed the effect of stereotaxic brain injection of human Alzheimer high-molecular-weight paired helical filaments (PHFs) in the dentate gyrus of wild-type and mutant tau THY-Tau22 mice. After 3 months of incubation, wild-type and THY-Tau22 mice developed an atrophy of the dentate gyrus and a tau pathology characterized by Gallyas and tau-positive grain-like inclusions into granule cells that extended in the hippocampal hilus and eventually away into the alveus, and the fimbria. Gallyas-positive neuropil threads and oligodendroglial coiled bodies were also observed. These tau inclusions were composed only of mouse tau, and were immunoreactive with antibodies to 4R tau, phosphotau, misfolded tau, ubiquitin, and p62. Although local hyperphosphorylation of tau was increased in the dentate gyrus in THY-Tau22 mice, the development of neurofibrillary tangles made of mutant human tau was not accelerated in the hippocampus, indicating that wild-type human PHFs were inefficient in seeding tau aggregates made of G272V/P301S mutant human tau. Our results indicate thus that injection of human wild-type Alzheimer PHF seeded aggregation of wild-type murine tau into an argyrophilic 4R tau pathology, and constitutes an interesting model independent of expression of a mutant tau protein.

  20. Search for a Low-Mass Higgs Boson in UPSILON(3S)->gammaA{sup 0}, A{sup 0}->tau{sup +}tau{sup -} at BABAR

    SciTech Connect

    Aubert, B.; Karyotakis, Y.; Lees, J. P.; Poireau, V.; Prencipe, E.; Prudent, X.; Tisserand, V.; 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.

    2009-10-30

    We search for a light Higgs boson A{sup 0} in the radiative decay UPSILON(3S)->gammaA{sup 0}, A{sup 0}->tau{sup +}tau{sup -}, tau{sup +}->e{sup +}nu{sub e}nu{sub tau}, or tau{sup +}->mu{sup +}nu{sub mu}nu{sub tau}. The data sample contains 122x10{sup 6} UPSILON(3S) events recorded with the BABAR detector. We find no evidence for a narrow structure in the studied tau{sup +}tau{sup -} invariant mass region of 4.03tau{sup +}}{sub tau{sup -}}<10.10 GeV/c{sup 2}. We exclude at the 90% confidence level (C.L.) a low-mass Higgs boson decaying to tau{sup +}tau{sup -} with a product branching fraction B(UPSILON(3S)->gammaA{sup 0})xB(A{sup 0}->tau{sup +}tau{sup -})>(1.5-16)x10{sup -5} across the m{sub tau}{sup +}{sub tau}{sup -} range. We also set a 90% C.L. upper limit on the tau{sup +}tau{sup -} decay of the eta{sub b} at B(eta{sub b}->tau{sup +}tau{sup -})<8%.

  1. High-Molecular-Weight Paired Helical Filaments from Alzheimer Brain Induces Seeding of Wild-Type Mouse Tau into an Argyrophilic 4R Tau Pathology in Vivo.

    PubMed

    Audouard, Emilie; Houben, Sarah; Masaracchia, Caterina; Yilmaz, Zehra; Suain, Valérie; Authelet, Michèle; De Decker, Robert; Buée, Luc; Boom, Alain; Leroy, Karelle; Ando, Kunie; Brion, Jean-Pierre

    2016-10-01

    In Alzheimer disease, the development of tau pathology follows neuroanatomically connected pathways, suggesting that abnormal tau species might recruit normal tau by passage from cell to cell. Herein, we analyzed the effect of stereotaxic brain injection of human Alzheimer high-molecular-weight paired helical filaments (PHFs) in the dentate gyrus of wild-type and mutant tau THY-Tau22 mice. After 3 months of incubation, wild-type and THY-Tau22 mice developed an atrophy of the dentate gyrus and a tau pathology characterized by Gallyas and tau-positive grain-like inclusions into granule cells that extended in the hippocampal hilus and eventually away into the alveus, and the fimbria. Gallyas-positive neuropil threads and oligodendroglial coiled bodies were also observed. These tau inclusions were composed only of mouse tau, and were immunoreactive with antibodies to 4R tau, phosphotau, misfolded tau, ubiquitin, and p62. Although local hyperphosphorylation of tau was increased in the dentate gyrus in THY-Tau22 mice, the development of neurofibrillary tangles made of mutant human tau was not accelerated in the hippocampus, indicating that wild-type human PHFs were inefficient in seeding tau aggregates made of G272V/P301S mutant human tau. Our results indicate thus that injection of human wild-type Alzheimer PHF seeded aggregation of wild-type murine tau into an argyrophilic 4R tau pathology, and constitutes an interesting model independent of expression of a mutant tau protein. PMID:27497324

  2. cuTauLeaping: A GPU-Powered Tau-Leaping Stochastic Simulator for Massive Parallel Analyses of Biological Systems

    PubMed Central

    Besozzi, Daniela; Pescini, Dario; Mauri, Giancarlo

    2014-01-01

    Tau-leaping is a stochastic simulation algorithm that efficiently reconstructs the temporal evolution of biological systems, modeled according to the stochastic formulation of chemical kinetics. The analysis of dynamical properties of these systems in physiological and perturbed conditions usually requires the execution of a large number of simulations, leading to high computational costs. Since each simulation can be executed independently from the others, a massive parallelization of tau-leaping can bring to relevant reductions of the overall running time. The emerging field of General Purpose Graphic Processing Units (GPGPU) provides power-efficient high-performance computing at a relatively low cost. In this work we introduce cuTauLeaping, a stochastic simulator of biological systems that makes use of GPGPU computing to execute multiple parallel tau-leaping simulations, by fully exploiting the Nvidia's Fermi GPU architecture. We show how a considerable computational speedup is achieved on GPU by partitioning the execution of tau-leaping into multiple separated phases, and we describe how to avoid some implementation pitfalls related to the scarcity of memory resources on the GPU streaming multiprocessors. Our results show that cuTauLeaping largely outperforms the CPU-based tau-leaping implementation when the number of parallel simulations increases, with a break-even directly depending on the size of the biological system and on the complexity of its emergent dynamics. In particular, cuTauLeaping is exploited to investigate the probability distribution of bistable states in the Schlögl model, and to carry out a bidimensional parameter sweep analysis to study the oscillatory regimes in the Ras/cAMP/PKA pathway in S. cerevisiae. PMID:24663957

  3. Absence of a Role for Phosphorylation in the Tau Pathology of Alzheimer’s Disease

    PubMed Central

    Lai, Robert Y. K.; Harrington, Charles R.; Wischik, Claude M.

    2016-01-01

    Alzheimer’s disease is characterized by redistribution of the tau protein pool from soluble to aggregated states. Aggregation forms proteolytically stable core polymers restricted to the repeat domain, and this binding interaction has prion-like properties. We have compared the binding properties of tau and tubulin in vitro using a system in which we can measure binding affinities for proteins alternated between solid and aqueous phases. The study reveals that a phase-shifted repeat domain fragment from the Paired Helical Filament core contains all that is required for high affinity tau-tau binding. Unlike tau-tubulin binding, tau-tau binding shows concentration-dependent enhancement in both phase directions due to an avidity effect which permits one molecule to bind to many as the concentration in the opposite phase increases. Phosphorylation of tau inhibits tau-tau binding and tau-tubulin binding to equivalent extents. Tau-tau binding is favoured over tau-tubulin binding by factors in the range 19–41-fold, irrespective of phosphorylation status. A critical requirement for tau to become aggregation-competent is prior binding to a solid-phase substrate, which induces a conformational change in the repeat domain permitting high-affinity binding to occur even if tau is phosphorylated. The endogenous species enabling this nucleation event to occur in vivo remains to be identified. The findings of the study suggest that development of disease-modifying drugs for tauopathies should not target phosphorylation, but rather should target inhibitors of tau-tau binding or inhibitors of the binding interaction with as yet unidentified endogenous polyanionic substrates required to nucleate tau assembly. PMID:27070645

  4. Tyrosine Nitration within the Proline-Rich Region of Tau in Alzheimer's Disease

    PubMed Central

    Reyes, Juan F.; Fu, Yifan; Vana, Laurel; Kanaan, Nicholas M.; Binder, Lester I.

    2011-01-01

    A substantial body of evidence suggests that nitrative injury contributes to neurodegeneration in Alzheimer's disease (AD) and other neurodegenerative disorders. Previously, we showed in vitro that within the tau protein the N-terminal tyrosine residues (Y18 and Y29) are more susceptible to nitrative modifications than other tyrosine sites (Y197 and Y394). Using site-specific antibodies to nitrated tau at Y18 and Y29, we identified tau nitrated in both glial (Y18) and neuronal (Y29) tau pathologies. In this study, we report the characterization of two novel monoclonal antibodies, Tau-nY197 and Tau-nY394, recognizing tau nitrated at Y197 and Y394, respectively. By Western blot analysis, Tau-nY197 labeled soluble tau and insoluble paired helical filament proteins (PHF-tau) nitrated at Y197 from control and AD brain samples. Tau-nY394 failed to label soluble tau isolated from control or severe AD samples, but labeled insoluble PHF-tau to a limited extent. Immunohistochemical analysis using Tau-nY197 revealed the hallmark tau pathology associated with AD; Tau-nY394 did not detect any pathological lesions characteristic of the disorder. These data suggest that a subset of the hallmark pathological inclusions of AD contain tau nitrated at Y197. However, nitration at Y197 was also identified in soluble tau from all control samples, including those at Braak stage 0, suggesting that nitration at this site in the proline-rich region of tau may have normal biological functions in the human brain. PMID:21514440

  5. Lepton-Flavor-Violation in tau-Production at BaBar - A Search for e+ e- to l+ tau-

    SciTech Connect

    Schenk, S.; /Heidelberg U.

    2007-10-26

    We report on a search for the lepton-flavor-violating processes e{sup +}e{sup -} {yields} {mu}{sup +}{tau}{sup -} and e{sup +}e{sup -} {yields} e{sup +}{tau}{sup -}. The data sample corresponds to an integrated luminosity of 211 fb{sup -1} recorded by the BABAR experiment at the SLAC PEP-II asymmetric-energy B Factory at a center-of-mass energy of {radical}s = 10:58 GeV. We find no evidence for a signal and set the 95% confidence level upper limits on the cross sections to be {sigma}{sub {mu}{tau}} < 4:6 fb and {sigma}{sub e{tau}} < 10:1 fb. The ratios of the cross sections with respect to the dimuon cross section are measured to be {sigma}{sub {mu}{tau}} ={sigma}{sub {mu}{mu}} < 4:0x10{sup -6} and {sigma}{sub e{tau}}/{sigma}{sub {mu}{mu}} < 8.9 x 10{sup -6}.

  6. Monte Carlo treatment of Lyman-alpha radiation in a plane-parallel atmosphere.

    NASA Technical Reports Server (NTRS)

    Modali, S. B.; Brandt, J. C.; Kastner, S. O.

    1972-01-01

    A Monte Carlo technique involving Stokes vectors is used to obtain the state of polarization and intensity of solar Lyman-alpha photons as they diffuse through a plane-parallel homogeneous model of earth's hydrogen envelope. Fine structure of Lyman-alpha and Doppler redistribution of frequencies are taken into account. Comparison of the results with Heath's observed upper limit for polarization of 1.5 per cent implies an optical thickness tau greater than 7 and intensities of 8-10 kilorayleighs for a solar Lyman-alpha flux of 5.8 ergs per sq cm per sec.

  7. Lepton Universality, |V(Us)| and Search for Second Class Current in Tau Decays

    SciTech Connect

    Banerjee, Swagato; /Victoria U.

    2011-11-10

    Several hundred million {tau} decays have been studied with the BABAR detector at the PEP-II e{sup +}e{sup -} collider at the SLAC National Accelerator Laboratory. Recent results on Charged Current Lepton Universality and two independent 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}}, K{sup -} {nu}{sub {tau}} and K{sub S}{sup 0}{pi}{sup -} {nu}{sub {tau}} decays, and a search for Second Class Current in {tau}{sup -} {yields} {pi}{sup -} {omega}{nu}{sub {tau}} decays are presented, where the charge conjugate decay modes are also implied.

  8. Evidence for the appearance of atmospheric tau neutrinos in super-Kamiokande.

    PubMed

    Abe, K; Hayato, Y; Iida, T; Iyogi, K; Kameda, J; Koshio, Y; Kozuma, Y; Marti, Ll; Miura, M; Moriyama, S; Nakahata, M; Nakayama, S; Obayashi, Y; Sekiya, H; Shiozawa, M; Suzuki, Y; Takeda, A; Takenaga, Y; Ueno, K; Ueshima, K; Yamada, S; Yokozawa, T; Ishihara, C; Kaji, H; Kajita, T; Kaneyuki, K; Lee, K P; McLachlan, T; Okumura, K; Shimizu, Y; Tanimoto, N; Labarga, L; Kearns, E; Litos, M; Raaf, J L; Stone, J L; Sulak, L R; Goldhaber, M; Bays, K; Kropp, W R; Mine, S; Regis, C; Renshaw, A; Smy, M B; Sobel, H W; Ganezer, K S; Hill, J; Keig, W E; Jang, J S; Kim, J Y; Lim, I T; Albert, J B; Scholberg, K; Walter, C W; Wendell, R; Wongjirad, T M; Ishizuka, T; Tasaka, S; Learned, J G; Matsuno, S; Smith, S N; Hasegawa, T; Ishida, T; Ishii, T; Kobayashi, T; Nakadaira, T; Nakamura, K; Nishikawa, K; Oyama, Y; Sakashita, K; Sekiguchi, T; Tsukamoto, T; Suzuki, A T; Takeuchi, Y; Ikeda, M; Minamino, A; Nakaya, T; Fukuda, Y; Itow, Y; Mitsuka, G; Tanaka, T; Jung, C K; Lopez, G D; Taylor, I; Yanagisawa, C; Ishino, H; Kibayashi, A; Mino, S; Mori, T; Sakuda, M; Toyota, H; Kuno, Y; Yoshida, M; Kim, S B; Yang, B S; Okazawa, H; Choi, Y; Nishijima, K; Koshiba, M; Yokoyama, M; Totsuka, Y; Martens, K; Schuemann, J; Vagins, M R; Chen, S; Heng, Y; Yang, Z; Zhang, H; Kielczewska, D; Mijakowski, P; Connolly, K; Dziomba, M; Thrane, E; Wilkes, R J

    2013-05-01

    Super-Kamiokande atmospheric neutrino data were fit with an unbinned maximum likelihood method to search for the appearance of tau leptons resulting from the interactions of oscillation-generated tau neutrinos in the detector. Relative to the expectation of unity, the tau normalization is found to be 1.42 ± 0.35(stat)(-0.12)(+0.14)(syst) excluding the no-tau-appearance hypothesis, for which the normalization would be zero, at the 3.8σ level. We estimate that 180.1 ± 44.3(stat)(-15.2)(+17.8) (syst) tau leptons were produced in the 22.5 kton fiducial volume of the detector by tau neutrinos during the 2806 day running period. In future analyses, this large sample of selected tau events will allow the study of charged current tau neutrino interaction physics with oscillation produced tau neutrinos.

  9. The abnormal phosphorylation of tau protein at Ser-202 in Alzheimer disease recapitulates phosphorylation during development.

    PubMed Central

    Goedert, M; Jakes, R; Crowther, R A; Six, J; Lübke, U; Vandermeeren, M; Cras, P; Trojanowski, J Q; Lee, V M

    1993-01-01

    Tau is a neuronal phosphoprotein whose expression is developmentally regulated. A single tau isoform is expressed in fetal human brain but six isoforms are expressed in adult brain, with the fetal isoform corresponding to the shortest of the adult isoforms. Phosphorylation of tau is also developmentally regulated, as fetal tau is phosphorylated at more sites than adult tau. In Alzheimer disease, the six adult tau isoforms become abnormally phosphorylated and form the paired helical filament, the major fibrous component of the characteristic neurofibrillary lesions. We show here that Ser-202 (in the numbering of the longest human brain tau isoform) is a phosphorylation site that distinguishes fetal from adult tau and we identify it as one of the abnormal phosphorylation sites in Alzheimer disease. The abnormal phosphorylation of tau at Ser-202 in Alzheimer disease thus recapitulates normal phosphorylation during development. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:8506352

  10. Measurement of the tau lepton mass by the Beijing Spectrometer (BES) Collaboration

    SciTech Connect

    Soderstrom, E.; BES Collaboration

    1992-11-01

    The mass of the {tau} lepton has been measured at the Beijing Electron Positron Collider using the Beijing Spectrometer. A search near threshold for e{sup +}e{sup {minus}} {yields} {tau}{sup +}{tau}{sup {minus}} was performed. Candidate events were identified by requiring that one {tau} decay via {tau} {yields} e{nu}{bar {nu}}, and the other via {tau} {yields} {mu}{nu}{bar {nu}}. The mass value, obtained from a fit to the energy dependence of the {tau}{sup +}{tau}{sup {minus}} cross section, is m{sub {tau}} = 1776.9{sub -0.5}{sup +0.4} {plus_minus} 0.2 MeV.

  11. Characterization of Early Pathological Tau Conformations and Phosphorylation in Chronic Traumatic Encephalopathy.

    PubMed

    Kanaan, Nicholas M; Cox, Kristine; Alvarez, Victor E; Stein, Thor D; Poncil, Sharra; McKee, Ann C

    2016-01-01

    Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy that develops after repetitive head injury. Several lines of evidence in other tauopathies suggest that tau oligomer formation induces neurotoxicity and that tau oligomer-mediated neurotoxicity involves induction of axonal dysfunction through exposure of an N-terminal motif in tau, the phosphatase-activating domain (PAD). Additionally, phosphorylation at serine 422 in tau occurs early and correlates with cognitive decline in patients with Alzheimer disease (AD). We performed immunohistochemistry and immunofluorescence on fixed brain sections and biochemical analysis of fresh brain extracts to characterize the presence of PAD-exposed tau (TNT1 antibody), tau oligomers (TOC1 antibody), tau phosphorylated at S422 (pS422 antibody), and tau truncated at D421 (TauC3 antibody) in the brains of 9-11 cases with CTE and cases of nondemented aged controls and AD (Braak VI) (n = 6, each). All 3 early tau markers (ie, TNT1, TOC1, and pS422) were present in CTE and displayed extensive colocalization in perivascular tau lesions that are considered diagnostic for CTE. Notably, the TauC3 epitope, which is abundant in AD, was relatively sparse in CTE. Together, these results provide the first description of PAD exposure, TOC1 reactive oligomers, phosphorylation of S422, and TauC3 truncation in the tau pathology of CTE. PMID:26671985

  12. Aging analysis reveals slowed tau turnover and enhanced stress response in a mouse model of tauopathy.

    PubMed

    Dickey, Chad; Kraft, Clara; Jinwal, Umesh; Koren, John; Johnson, Amelia; Anderson, Laura; Lebson, Lori; Lee, Daniel; Dickson, Dennis; de Silva, Rohan; Binder, Lester I; Morgan, David; Lewis, Jada

    2009-01-01

    We have extensively analyzed the biochemical and histochemical profiles of the tau protein from the rTg4510 transgenic mouse model in which the animals uniquely develop forebrain tau pathologies similar to those found in human tauopathies. Levels of several soluble phosphorylated tau species were highest at 1 month relative to later time points, suggesting that certain tau hyperphosphorylation events were insufficient to drive tangle formation in young mice. Despite a robust, pre-tangle-like accumulation of phospho-tau in 1-month-old mice, this material was cleared by 3 months, indicating that the young mouse brain either fails to facilitate tau insolubility or possesses an enhanced ability to clear tau relative to the adult. We also found that while heat shock protein expression increased with normal aging, this process was accelerated in rTg4510 mice. Moreover, by exploiting an exon 10 (-) specific antibody, we demonstrated that endogenous mouse tau turnover was slowed in response to human tau over-expression, and that this endogenous tau adopted disease-related properties. These data suggest that a younger brain fails to develop lasting tau pathology despite elevated levels of phosphorylated tau, perhaps because of reduced expression of stress-related proteins. Moreover, we show that the active production of small amounts of abnormal tau protein facilitates dysfunction and accumulation of otherwise normal tau, a significant implication for the pathogenesis of patients with Alzheimer's disease.

  13. Trans-Synaptic Spread of Tau Pathology In Vivo

    PubMed Central

    Liu, Li; Drouet, Valerie; Wu, Jessica W.; Witter, Menno P.; Small, Scott A.; Clelland, Catherine; Duff, Karen

    2012-01-01

    Tauopathy in the brain of patients with Alzheimer's disease starts in the entorhinal cortex (EC) and spreads anatomically in a defined pattern. To test whether pathology initiating in the EC spreads through the brain along synaptically connected circuits, we have generated a transgenic mouse model that differentially expresses pathological human tau in the EC and we have examined the distribution of tau pathology at different timepoints. In relatively young mice (10–11 months old), human tau was present in some cell bodies, but it was mostly observed in axons within the superficial layers of the medial and lateral EC, and at the terminal zones of the perforant pathway. In old mice (>22 months old), intense human tau immunoreactivity was readily detected not only in neurons in the superficial layers of the EC, but also in the subiculum, a substantial number of hippocampal pyramidal neurons especially in CA1, and in dentate gyrus granule cells. Scattered immunoreactive neurons were also seen in the deeper layers of the EC and in perirhinal and secondary somatosensory cortex. Immunoreactivity with the conformation-specific tau antibody MC1 correlated with the accumulation of argyrophilic material seen in old, but not young mice. In old mice, axonal human tau immunoreactivity, especially at the endzones of the perforant pathway, was greatly reduced. Relocalization of tau from axons to somatodendritic compartments and propagation of tauopathy to regions outside of the EC correlated with mature tangle formation in neurons in the EC as revealed by thioflavin-S staining. Our data demonstrate propagation of pathology from the EC and support a trans-synaptic mechanism of spread along anatomically connected networks, between connected and vulnerable neurons. In general, the mouse recapitulates the tauopathy that defines the early stages of AD and provides a model for testing mechanisms and functional outcomes associated with disease progression. PMID:22312444

  14. Planet formation in multiple stellar systems: GG Tau A

    NASA Astrophysics Data System (ADS)

    Di Folco, E.; Dutrey, A.; Guilloteau, S.; Le Bouquin, J.-B.; Lacour, S.; Berger, J.-P.; Köhler, R.; Piétu, V.

    2014-12-01

    GG Tau is a hierarchical quadruple system of young, low-mass stars. Because of its well-studied bright circumbinary ring of dust and gas surrounding the main binary GG Tau A, it is a unique laboratory to study planet formation in the disturbed environment of binary/multiple stellar systems. We have started a large observing program of GG Tau A that combines several high-resolution instruments in a multi-wavelength approach. We have recently reported the detection of a new low-mass companion in GG Tau A that turns out to itself be a triple system. This discovery was possible thanks to the very high angular resolution of the near-IR instrument PIONIER on the VLT interferometer, and was confirmed with sub-aperture masking techniques on VLT/NaCo. The detected close binary GG Tau Ab (ρ = 0.032'', or about 5 AU) provides a natural explanation for two enigmas: the discrepancy between the dynamical mass and the spectral type estimates in GG Tau A, and the absence of dust thermal emission in the vicinity of the Ab component. GRAVITY will provide the adequate angular resolution to complete the astrometric characterization of the close binary in the next 10 years. With now 5 coeval low-mass stars, GG Tau is an ideal laboratory to calibrate stellar evolution tracks at young ages (few Myr). Beyond this peculiar system, GRAVITY also has a strong potential to study the impact of multiplicity on the existence of disks, and in fine on planet formation mechanisms in multiple systems.

  15. A search for the production of the final states. tau. sup +. tau. sup minus e sup + e sup minus ,. tau. sup +. tau. sup minus. mu. sup +. mu. sup minus , and. tau. sup +. tau. sup minus. pi. sup +. pi. sup minus in e sup + e sup minus collisions at radical s = 29 GeV

    SciTech Connect

    Not Available

    1991-07-01

    We have searched for the reaction e{sup +}e{sup {minus}} {yields} {tau}{sup +}{tau}{sup {minus}}{bar f}f, where f is either an electron, muon, or charged pion, at {radical}s = 29 GeV using the Mark 2 detector at the PEP storage ring. One candidate event is found while 2.3 events are expected from known processes. We would expect to see 11 events if the cross-section for e{sup +}e{sup {minus}} {yields} {tau}{sup +}{tau}{sup {minus}}{bar f}f at {radical}s = 29 GeV were enhanced by the factor of 4.7 which the ALEPH collaboration reports for {radical}s = 91 GeV. we also look for e{sup +}e{sup {minus}} {yields} e{sup +}e{sup {minus}}{bar f}f and e{sup +}e{sup {minus}} {yields} {mu}{sup +}{mu}{sup {minus}} {bar f}f, and for e{sup +}e{sup {minus}} {yields} {tau}{sup +}{tau}{sup {minus}} {gamma} using a similar analysis procedure and see the number of events predicted by the standard model. 10 refs., 5 figs., 3 tabs.

  16. ELISA measurement of specific antibodies to phosphorylated tau in intravenous immunoglobulin products.

    PubMed

    Loeffler, David A; Klaver, Andrea C; Coffey, Mary P

    2015-10-01

    The therapeutic effects of intravenous immunoglobulin (IVIG) products were recently studied in Alzheimer's disease (AD) patients. Pilot studies produced encouraging results but phase II and III trials gave disappointing results; a further study is in progress. IVIG products contain antibodies to tau protein, the main component of neurofibrillary tangles (NFTs). The tau used to detect IVIG's anti-tau antibodies in previous studies was non-phosphorylated recombinant human tau-441, but NFT-associated tau is extensively phosphorylated. The objective of this study was to determine if various IVIG products contain specific antibodies to phosphorylated tau (anti-pTau antibodies). ELISAs were used to evaluate binding of six IVIG products to a 12 amino acid peptide, tau 196-207, which was phosphorylated ("pTau peptide") or non-phosphorylated ("non-pTau peptide") at Serine-199 and Serine-202. Both amino acid residues are phosphorylated in AD NFTs. Each IVIG's "anti-pTau antibody ratio" was calculated by dividing its binding to the pTau peptide by its binding to the non-pTau peptide. Seven experiments were performed and data were pooled, with each experiment contributing one data point from each IVIG product. Mean anti-pTau antibody ratios greater than 1.0, suggesting specific antibodies to phosphorylated tau, were found for three IVIG products. Because administration of antibodies to phosphorylated tau has been found to reduce tau-associated pathology in transgenic mouse models of tauopathy, increasing the levels of anti-pTau antibodies, together with other selected antibodies such as anti-Aβ, in IVIG might increase its ability to slow AD's progression.

  17. Tau phosphorylation at serine 396 residue is required for hippocampal LTD.

    PubMed

    Regan, Philip; Piers, Thomas; Yi, Jee-Hyun; Kim, Dong-Hyun; Huh, Seonghoo; Park, Se Jin; Ryu, Jong Hoon; Whitcomb, Daniel J; Cho, Kwangwook

    2015-03-25

    Tau is required for the induction of long-term depression (LTD) of synaptic transmission in the hippocampus. Here we probe the role of tau in LTD, finding that an AMPA receptor internalization mechanism is impaired in tau KO mice, and that LTD causes specific phosphorylation at the serine 396 and 404 residues of tau. Surprisingly, we find that phosphorylation at serine 396, specifically, is critical for LTD but has no role in LTP. Finally, we show that tau KO mice exhibit deficits in spatial reversal learning. These findings underscore the physiological role for tau at the synapse and identify a behavioral correlate of its role in LTD. PMID:25810511

  18. Phospholipids block nuclear factor-kappa B and tau phosphorylation and inhibit amyloid-beta secretion in human neuroblastoma cells.

    PubMed

    Pandey, N R; Sultan, K; Twomey, E; Sparks, D L

    2009-12-29

    Inflammation and oxidative stress have been shown to play a critical role in the pathophysiology that leads to neurodegeneration. Omega-6 phospholipids, e.g. dilinoleoylphosphatidylcholine (DLPC), have been shown to have anti-inflammatory properties and therefore experiments were undertaken to determine whether DLPC can prevent inflammatory neurodegenerative events in the model neuronal cell line, SH-SY5Y. Tumor necrosis factor (TNF-alpha) and H(2)O(2) activate mitogen-activated protein kinase (MAPK) in SH-SY5Y cells within 5 min and this activation is completely blocked by DLPC (12 microM). DLPC blocks IkappaBalpha phosphorylation in the SH-SY5Y cells and prevents the phosphorylation and activation of nuclear factor-kappa B (NF-kappaB). The phospholipid inhibits induction of MAPK and NF-kappaB in similar fashion to the MEK1/2-inhibitor, U0126 (10 microM). DLPC completely abolishes TNF-alpha, H(2)O(2) and lipopolysaccaride (LPS)-induced neuronal tau phosphorylation. Cellular amyloid precursor protein levels are reduced by DLPC and LPS-induced amyloid-beta expression and secretion in SH-SY5Y cells are completely blocked by DLPC. Taken together, these data suggest that DLPC can act through MAPK to block neuronal inflammatory cascades and prevent potential pathological consequences in the neuronal metabolism of amyloid and tau proteins. PMID:19788916

  19. Observations of AA Tau requested to schedule XMM-Newton

    NASA Astrophysics Data System (ADS)

    Waagen, Elizabeth O.

    2013-08-01

    Dr. Hans Moritz Guenther (Harvard-Smithsonian Center for Astrophysics) has requested nightly observations of the classical T Tauri star AA Tau in order to schedule x-ray observations with XMM-Newton that have been planned for between 2013 August 15 and September 15. The purpose of the AAVSO observations is to determine whether AA Tau is at a suitable magnitude for the satellite observations. Taurus is difficult to observe during this time period but that is exactly why AAVSO assistance is needed! AA Tau is a morning object, and also, many of the professional ground-based telescopes are offline because of the US southwest monsoon season. Since it is critical to know the brightness of AA Tau, AAVSO observations will be truly essential. Nightly visual and snapshot (not more than once per night) observations beginning now and continuing through September 20 are needed. Coverage beginning ahead of the XMM window is requested because there is a one- to two-week lead time for the target to be inserted into the telescope schedule. Continuing the nightly observations a few days beyond the end of the XMM window will give better optical context for the x-ray data. AA Tau ranges between ~12.8V and ~16.1V; since December 2011 or earlier it has been at ~14.5V. The most recent observation in the AAVSO International Database shows it at 14.779V on 2013 Feb 5 (J. Roe, Bourbon, MO). Dr. Guenther writes, "AA Tau is surrounded by a thick accretion disk which is seen nearly edge-on. For decades the light curve of AA Tau showed regular eclipsing events when the accretion funnel rotated through the line of sight. However, earlier this year J. Bouvier and his group found that this behavior changed dramatically: AA Tau now seems to be deeply absorbed all the time (V band 14.5 mag). In collaboration with this group we will perform X-ray observations of AA Tau with the XMM-Newton satellite." Finder charts with sequence may be created using the AAVSO Variable Star Plo! tter (http

  20. Multinomial tau-leaping method for stochastic kinetic simulations.

    PubMed

    Pettigrew, Michel F; Resat, Haluk

    2007-02-28

    We introduce the multinomial tau-leaping (MtauL) method for general reaction networks with multichannel reactant dependencies. The MtauL method is an extension of the binomial tau-leaping method where efficiency is improved in several ways. First, tau-leaping steps are determined simply and efficiently using a priori information and Poisson distribution-based estimates of expectation values for reaction numbers over a tentative tau-leaping step. Second, networks are partitioned into closed groups of reactions and corresponding reactants in which no group reactant set is found in any other group. Third, product formation is factored into upper-bound estimation of the number of times a particular reaction occurs. Together, these features allow larger time steps where the numbers of reactions occurring simultaneously in a multichannel manner are estimated accurately using a multinomial distribution. Furthermore, we develop a simple procedure that places a specific upper bound on the total reaction number to ensure non-negativity of species populations over a single multiple-reaction step. Using two disparate test case problems involving cellular processes--epidermal growth factor receptor signaling and a lactose operon model--we show that the tau-leaping based methods such as the MtauL algorithm can significantly reduce the number of simulation steps thus increasing the numerical efficiency over the exact stochastic simulation algorithm by orders of magnitude. PMID:17343434

  1. Structure-activity relationship of cyanine tau aggregation inhibitors

    PubMed Central

    Chang, Edward; Congdon, Erin E.; Honson, Nicolette S.; Duff, Karen E.; Kuret, Jeff

    2009-01-01

    A structure-activity relationship for symmetrical cyanine inhibitors of human tau aggregation was elaborated using a filter trap assay. Antagonist activity depended on cyanine heterocycle, polymethine bridge length, and the nature of meso- and N-substituents. One potent member of the series, 3,3’-diethyl-9-methylthiacarbocyanine iodide (compound 11), retained submicromolar potency and had calculated physical properties consistent with blood-brain barrier and cell membrane penetration. Exposure of organotypic slices prepared from JNPL3 transgenic mice (which express human tau harboring the aggregation prone P301L tauopathy mutation) to compound 11 for one week revealed a biphasic dose response relationship. Low nanomolar concentrations decreased insoluble tau aggregates to half those observed in slices treated with vehicle alone. In contrast, high concentrations (≥300 nM) augmented tau aggregation and produced abnormalities in tissue tubulin levels. These data suggest that certain symmetrical carbocyanine dyes can modulate tau aggregation in the slice biological model at concentrations well below those associated with toxicity. PMID:19432420

  2. Multiple-motor based transport and its regulation by Tau

    PubMed Central

    Vershinin, Michael; Carter, Brian C.; Razafsky, David S.; King, Stephen J.; Gross, Steven P.

    2007-01-01

    Motor-based intracellular transport and its regulation are crucial to the functioning of a cell. Disruption of transport is linked to Alzheimer's and other neurodegenerative diseases. However, many fundamental aspects of transport are poorly understood. An important issue is how cells achieve and regulate efficient long-distance transport. Mounting evidence suggests that many in vivo cargoes are transported along microtubules by more than one motor, but we do not know how multiple motors work together or can be regulated. Here we first show that multiple kinesin motors, working in conjunction, can achieve very long distance transport and apply significantly larger forces without the need of additional factors. We then demonstrate in vitro that the important microtubule-associated protein, tau, regulates the number of engaged kinesin motors per cargo via its local concentration on microtubules. This function of tau provides a previously unappreciated mechanism to regulate transport. By reducing motor reattachment rates, tau affects cargo travel distance, motive force, and cargo dispersal. We also show that different isoforms of tau, at concentrations similar to those in cells, have dramatically different potency. These results provide a well defined mechanism for how altered tau isoform levels could impair transport and thereby lead to neurodegeneration without the need of any other pathway. PMID:17190808

  3. Tau Based Therapeutic Approaches for Alzheimer’s Disease

    PubMed Central

    Boutajangout, Allal; Wisniewski, Thomas

    2014-01-01

    The accumulation of aggregated, hyperphosphorylated tau as neurofibrillary tangles (NFTs) and neuropil threads (NT) are cardinal features of Alzheimer’s disease (AD). The other lesions found in AD include amyloid plaques and congophilic amyloid angiopathy, both associated with the extracellular accumulation of the amyloid β (Aβ) peptide. AD is the most common cause of dementia globally. Currently there are no effective means to treat AD or even to slow it down. The dominant theory for the causation of AD is the amyloid cascade hypothesis, which suggests that the aggregation of Aβ as oligomers and amyloid plaques is central to the pathogenesis of AD. Numerous therapies have been developed directed to Aβ relate pathology, in particular various immunotherapeutic approaches. So far all of these have failed in clinical trials. Recently there has been more focus on therapy directed to tau related pathology, which correlates better with the cognitive status of patients, compared to the amyloid burden. Immunotherapeutic targeting of tau pathology has showed great potential to treat tau pathologies in mouse models of AD. A number of studies have shown the efficacy of both passive and active immunization. This review summarizes recent advances on therapy targeting pathological tau protein, in particular focusing on immunotherapeutic approaches which are showing great promise. PMID:24732638

  4. Oligomerization of the protein tau in the Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Larini, Luca

    The Alzheimer's disease is characterized by the formation of protein aggregates both within and outside of the brain's cells, the neurons. Within the neurons, the aggregation of the microtubule associated protein tau leads to the destruction of the microtubules in the axon of the neuron. Tau is extremely flexible and is classified as an intrinsically disordered protein due to its low propensity to form secondary structure. Tau promotes tubulin assembly into microtubules, which are an essential component of the cytoskeleton of the axon. The microtubule binding region of tau consists of 4 pseudo-repeats that are critical for aggregation as well. In this study, we focus on the aggregation propensity of different segments of the microtubule binding region as well as post-translational modifications that can alter tau dynamics and structure. We have performed replica exchange molecular dynamics simulations to characterize the ensemble of conformations of the monomer and small oligomers as well as how these structures are stabilized or destabilized by mutations and post-translational modifications.

  5. 3D Visualization of the Temporal and Spatial Spread of Tau Pathology Reveals Extensive Sites of Tau Accumulation Associated with Neuronal Loss and Recognition Memory Deficit in Aged Tau Transgenic Mice

    PubMed Central

    Fu, Hongjun; Hussaini, S. Abid; Wegmann, Susanne; Profaci, Caterina; Daniels, Jacob D.; Herman, Mathieu; Emrani, Sheina; Figueroa, Helen Y.; Hyman, Bradley T.; Davies, Peter; Duff, Karen E.

    2016-01-01

    3D volume imaging using iDISCO+ was applied to observe the spatial and temporal progression of tau pathology in deep structures of the brain of a mouse model that recapitulates the earliest stages of Alzheimer’s disease (AD). Tau pathology was compared at four timepoints, up to 34 months as it spread through the hippocampal formation and out into the neocortex along an anatomically connected route. Tau pathology was associated with significant gliosis. No evidence for uptake and accumulation of tau by glia was observed. Neuronal cells did appear to have internalized tau, including in extrahippocampal areas as a small proportion of cells that had accumulated human tau protein did not express detectible levels of human tau mRNA. At the oldest timepoint, mature tau pathology in the entorhinal cortex (EC) was associated with significant cell loss. As in human AD, mature tau pathology in the EC and the presence of tau pathology in the neocortex correlated with cognitive impairment. 3D volume imaging is an ideal technique to easily monitor the spread of pathology over time in models of disease progression. PMID:27466814

  6. Ozonolysis of the double bond of the unsaturated uronate residue in low-molecular-weight heparin and K5 heparosan.

    PubMed

    Masuko, Sayaka; Higashi, Kyohei; Wang, Zhenyu; Bhaskar, Ujjwal; Hickey, Anne Marie; Zhang, Fuming; Toida, Toshihiko; Dordick, Jonathan S; Linhardt, Robert J

    2011-09-27

    Ozone is known to add across and cleave carbon-carbon double bonds. Ozonolysis is widely used for the preparation of pharmaceuticals, for bleaching substances and for killing microorganisms in air and water sources. Some polysaccharides and oligosaccharides, such as those prepared using chemical or enzymatic β-elimination, contain a site of unsaturation. We examined ozonolysis of low-molecular-weight heparins (LMWHs), enoxaparin and logiparin, and heparosan oligo- and polysaccharides for the removal of the nonreducing terminal unsaturated uronate residue. 1D (1)H NMR showed that these ozone-treated polysaccharides retained the same structure as the starting polysaccharide, except that the C4-C5 double bond in the nonreducing end unsaturated uronate had been removed. The anticoagulant activity of the resulting product from enoxaparin and logiparin was comparable to that of the starting material. These results demonstrate that ozonolysis is an important tool for the removal of unsaturated uronate residues from LMWHs and heparosan without modification of the core polysaccharide structure or diminution of anticoagulant activity. This reaction also has potential applications in the chemoenzymatic synthesis of bioengineered heparin from Escherichia coli-derived K5 heparosan.

  7. Passive immunization targeting the N-terminal projection domain of tau decreases tau pathology and improves cognition in a transgenic mouse model of Alzheimer disease and tauopathies.

    PubMed

    Dai, Chun-ling; Chen, Xia; Kazim, Syed Faraz; Liu, Fei; Gong, Cheng-Xin; Grundke-Iqbal, Inge; Iqbal, Khalid

    2015-04-01

    Intraneuronal accumulation of abnormally hyperphosphorylated tau in the brain is a histopathological hallmark of Alzheimer's disease and a family of related neurodegenerative disorders collectively called tauopathies. At present there is no effective treatment available for these progressive neurodegenerative diseases which are clinically characterized by dementia in mid to old-age. Here we report the treatment of 14-17-months-old 3xTg-AD mice with tau antibodies 43D (tau 6-18) and 77E9 (tau 184-195) to the N-terminal projection domain of tau or mouse IgG as a control by intraperitoneal injection once a week for 4 weeks, and the effects of the passive immunization on reduction of hyperphosphorylated tau, Aβ accumulation and cognitive performance in these animals. We found that treatment with tau antibodies 43D and 77E9 reduced total tau level, decreased tau hyperphosphorylated at Ser199, Ser202/Thr205 (AT8), Thr205, Ser262/356 (12E8), and Ser396/404 (PHF-1) sites, and a trend to reduce Aβ pathology. Most importantly, targeting N-terminal tau especially by 43D (tau 6-18) improved reference memory in the Morris water maze task in 3xTg-AD mice. We did not observe any abnormality in general physical characteristics of the treated animals with either of the two antibodies during the course of this study. Taken together, our studies demonstrate for the first time (1) that passive immunization targeting normal tau can effectively clear the hyperphosphorylated protein and possibly reduce Aβ pathology from the brain and (2) that targeting N-terminal projection domain of tau containing amino acid 6-18 is especially beneficial. Thus, targeting selective epitopes of N-terminal domain of tau may present a novel effective therapeutic opportunity for Alzheimer disease and other tauopathies.

  8. Nuclear magnetic resonance spectroscopy characterization of interaction of Tau with DNA and its regulation by phosphorylation.

    PubMed

    Qi, Haoling; Cantrelle, François-Xavier; Benhelli-Mokrani, Houda; Smet-Nocca, Caroline; Buée, Luc; Lippens, Guy; Bonnefoy, Eliette; Galas, Marie-Christine; Landrieu, Isabelle

    2015-02-24

    The capacity of endogenous Tau to bind DNA has been recently identified in neurons under physiological or oxidative stress conditions. Characterization of the protein domains involved in Tau-DNA complex formation is an essential first step in clarifying the contribution of Tau-DNA interactions to neurological biological processes. To identify the amino acid residues involved in the interaction of Tau with oligonucleotides, we have characterized a Tau-DNA complex using nuclear magnetic resonance spectroscopy. Interaction of an AT-rich or GC-rich 22 bp oligonucleotide with Tau showed multiple points of anchoring along the intrinsically disordered Tau protein. The main sites of contact characterized here correspond to the second half of the proline-rich domain (PRD) of Tau and the R2 repeat in the microtubule binding domain. This latter interaction site includes the PHF6* sequence known to govern Tau aggregation. The characterization was pursued by studying the binding of phosphorylated forms of Tau, displaying multiple phosphorylation sites mainly in the PRD, to the same oligonucleotide. No interaction of phospho-Tau with the oligonucleotide was detected, suggesting that pathological Tau phosphorylation could affect the physiological function of Tau mediated by DNA binding.

  9. Tau antagonizes end-binding protein tracking at microtubule ends through a phosphorylation-dependent mechanism.

    PubMed

    Ramirez-Rios, Sacnicte; Denarier, Eric; Prezel, Eléa; Vinit, Angélique; Stoppin-Mellet, Virginie; Devred, François; Barbier, Pascale; Peyrot, Vincent; Sayas, Carmen Laura; Avila, Jesus; Peris, Leticia; Andrieux, Annie; Serre, Laurence; Fourest-Lieuvin, Anne; Arnal, Isabelle

    2016-10-01

    Proper regulation of microtubule dynamics is essential for cell functions and involves various microtubule-associated proteins (MAPs). Among them, end-binding proteins (EBs) accumulate at microtubule plus ends, whereas structural MAPs bind along the microtubule lattice. Recent data indicate that the structural MAP tau modulates EB subcellular localization in neurons. However, the molecular determinants of EB/tau interaction remain unknown, as is the effect of this interplay on microtubule dynamics. Here we investigate the mechanisms governing EB/tau interaction in cell-free systems and cellular models. We find that tau inhibits EB tracking at microtubule ends. Tau and EBs form a complex via the C-terminal region of EBs and the microtubule-binding sites of tau. These two domains are required for the inhibitory activity of tau on EB localization to microtubule ends. Moreover, the phosphomimetic mutation S262E within tau microtubule-binding sites impairs EB/tau interaction and prevents the inhibitory effect of tau on EB comets. We further show that microtubule dynamic parameters vary, depending on the combined activities of EBs and tau proteins. Overall our results demonstrate that tau directly antagonizes EB function through a phosphorylation-dependent mechanism. This study highlights a novel role for tau in EB regulation, which might be impaired in neurodegenerative disorders.

  10. Search for Tau-Lepton Decays to Seven Or More Pions With BaBar

    SciTech Connect

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

    2007-11-02

    We report the results of searches for several decay modes of the {tau}-lepton with {ge} 7 pions in the final state using 207 x 10{sup 6} {tau}-pairs collected with the BaBar detector. For the decays with 7 charged pions in the final state we find the following 90% CL upper limits: B({tau}{sup -} {yields} 4{pi}{sup -}3{pi}{sup +}({pi}{sup 0}){nu}{sub {tau}}) < 3.0 x 10{sup -7}, B({tau}{sup -} {yields} 4{pi}{sup -}3{pi}{sup +}{nu}{sub {tau}}) < 4.3 x 10{sup -7} and B({tau}{sup -} {yields}) B({tau}{sup -} {yields} 4{pi}{sup -}3{pi}{sup +}{pi}{sup 0}{nu}{sub {tau}}) < 2.5 x 10{sup -7}. We also search for the decay {tau}{sup -} {yields} 3{pi}{sup -}2{pi}{sup +}2{pi}{sup 0}{nu}{sub {tau}} and report a 90% CL upper limit of < 3.4 x 10{sup -6} for its branching fraction. Finally, we search for the exclusive final state {tau}{sup -} {yields} 2{sigma}{pi}{sup -}{nu}{sub {tau}} and find a 90% CL upper limit for its branching fraction of < 5.4 x 10{sup -7}.

  11. Measurement of the branching fraction for $\\tau\\to\\eta K\

    SciTech Connect

    del Amo Sanchez, P.; Lees, J.P.; Poireau, V.; Prencipe, E.; Tisserand, V.; Garra Tico, J.; Grauges, E.; Martinelli, M.; Palano, A.; Pappagallo, M.; Eigen, G.; Stugu, B.; Sun, L.; Battaglia, M.; Brown, D.N.; Hooberman, B.; Kerth, L.T.; Kolomensky, Yu.G.; Lynch, G.; Osipenkov, I.L.; Tanabe, T.; /UC, Berkeley /Birmingham U. /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. /Paris U., VI-VII /LLNL, Livermore /Liverpool U. /Queen Mary, U. of London /Royal Holloway, 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 /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

    2011-08-12

    The authors report on analyses of tau lepton decays {tau}{sup -} {yields} {eta}K{sup -}{nu}{sub {tau}} and {tau}{sup -} {yields} {eta}{pi}{sup -}{nu}{sub {tau}}, with {eta} {yields} {pi}{sup +}{pi}{sup -}{pi}{sup 0}, using 470 fb{sup -1} of data from the BABAR experiment at PEP-II, collected at center-of-mass energies at and near the {Upsilon}(4S) resonance. They measure the branching fraction for the {tau}{sup -} {yields} {eta}K{sup -}{nu}{sub {tau}} decay mode, {Beta}({tau}{sup -} {yields} {eta}K{sup -}{nu}{sub {tau}}) = (1.42 {+-} 0.11(stat) {+-} 0.07(syst)) x 10{sup -4}, and report a 95% confidence level upper limit for the second-class current process {tau}{sup -} {yields} {eta}{pi}{sup -}{nu}{sub {tau}}, {Beta}({tau}{sup -} {yields} {eta}{pi}{sup -}{nu}{sub {tau}}) < 9.9 x 10{sup -5}.

  12. Monitoring of Intracellular Tau Aggregation Regulated by OGA/OGT Inhibitors

    PubMed Central

    Lim, Sungsu; Haque, Md. Mamunul; Nam, Ghilsoo; Ryoo, Nayeon; Rhim, Hyewhon; Kim, Yun Kyung

    2015-01-01

    Abnormal phosphorylation of tau has been considered as a key pathogenic mechanism inducing tau aggregation in multiple neurodegenerative disorders, collectively called tauopathies. Recent evidence showed that tau phosphorylation sites are protected with O-linked β-N-acetylglucosamine (O-GlcNAc) in normal brain. In pathological condition, tau is de-glycosylated and becomes a substrate for kinases. Despite the importance of O-GlcNAcylation in tau pathology, O-GlcNAc transferase (OGT), and an enzyme catalyzing O-GlcNAc to tau, has not been carefully investigated in the context of tau aggregation. Here, we investigated intracellular tau aggregation regulated by BZX2, an inhibitor of OGT. Upon the inhibition of OGT, tau phosphorylation increased 2.0-fold at Ser199 and 1.5-fold at Ser396, resulting in increased tau aggregation. Moreover, the BZX2 induced tau aggregation was efficiently reduced by the treatment of Thiamet G, an inhibitor of O-GlcNAcase (OGA). Our results demonstrated the protective role of OGT in tau aggregation and also suggest the counter-regulatory mechanism of OGA and OGT in tau pathology. PMID:26343633

  13. Search for Lepton Flavor Violating Decays Tau+- to L+- Omega

    SciTech Connect

    Schenk, S.; /Heidelberg U.

    2011-11-30

    This paper reports on a search for lepton flavor violating decays of a {tau} lepton to a lighter-mass charged lepton and an {omega} vector meson. The data sample corresponds to an integrated luminosity of 384 fb{sup -1} recorded by the BaBar experiment at the SLAC PEP-II asymmetric-energy B Factory. No evidence for a signal is found and the upper limits on the branching ratios are determined to be B({tau}{sup {+-}} {yields} e{sup {+-}}{omega}) < 1.1 x 10{sup -7} and B({tau}{sup {+-}} {yields} {mu}{sup {+-}}{omega}) < 1.0 x 10{sup -7} at 90% confidence level.

  14. Direct cellular delivery of human proteasomes to delay tau aggregation.

    PubMed

    Han, Dong Hoon; Na, Hee-Kyung; Choi, Won Hoon; Lee, Jung Hoon; Kim, Yun Kyung; Won, Cheolhee; Lee, Seung-Han; Kim, Kwang Pyo; Kuret, Jeff; Min, Dal-Hee; Lee, Min Jae

    2014-01-01

    The 26S proteasome is the primary machinery that degrades ubiquitin (Ub)-conjugated proteins, including many proteotoxic proteins implicated in neurodegeneraton. It has been suggested that the elevation of proteasomal activity is tolerable to cells and may be beneficial to prevent the accumulation of protein aggregates. Here we show that purified proteasomes can be directly transported into cells through mesoporous silica nanoparticle-mediated endocytosis. Proteasomes that are loaded onto nanoparticles through non-covalent interactions between polyhistidine tags and nickel ions fully retain their proteolytic activity. Cells treated with exogenous proteasomes are more efficient in degrading overexpressed human tau than endogenous proteasomal substrates, resulting in decreased levels of tau aggregates. Moreover, exogenous proteasome delivery significantly promotes cell survival against proteotoxic stress caused by tau and reactive oxygen species. These data demonstrate that increasing cellular proteasome activity through the direct delivery of purified proteasomes may be an effective strategy for reducing cellular levels of proteotoxic proteins. PMID:25476420

  15. Effects of Tau on Flow-Aligned Microtubule Bundles

    NASA Astrophysics Data System (ADS)

    Ross, Jennifer L.; Kuchnir Fygenson, D.

    2003-03-01

    Microtubules are cylindrical crystals of the protein tubulin with 17nm inner diameter and 25nm outer diameter. Recent structural studies suggest that the microtubule wall may be porous to small molecules. We have investigated the mobility of molecules in bundles of flow aligned microtubules. We find the spacing between the microtubules in the bundle is increased by the addition of tau, a microtubule associated protein. In the absence of tau, flow can be used to make tightly packed bundles of microtubules. Adding tau causes the tight bundles to swell and separate. We use fluorescence recovery after photobleaching (FRAP) to quantify the mobility of a taxol, a small drug that binds to the microtubule interior.

  16. Challenging accretion models with an HETG observation of T Tau

    NASA Astrophysics Data System (ADS)

    Schneider, Christian

    2014-09-01

    Young, accreting stars often emit soft X-rays from the accretion shock on the stellar surface. The favored model predicts high densities in the accretion spot compatible with most observations. However, X-ray data of the nearest accreting star (TW Hya) and of the eponymous T Tau show signatures incompatible with shock models. Proposed model modifications require an enhanced density of higher temperature tracers compared to cooler plasma. We propose to test this with a 130 ks HETG observation of T Tau to (a) provide the first significant measurement of its Ne IX triplet (high temperature) to augment XMM-Newton data of the O VII triplet (low temperature) and (b) to search for spatial offsets of the soft X-rays which could explain the lack of accretion signatures in T Tau by jet emission.

  17. Bilocal expansion of the Borel amplitude and the hadronic tau decay width

    SciTech Connect

    Cvetic, Gorazd; Lee, Taekoon

    2001-07-01

    The singular part of the Borel transform of a QCD amplitude near the infrared renormalon can be expanded in terms of higher order Wilson coefficients of the operators associated with the renormalon. In this paper we observe that this expansion gives nontrivial constraints on the Borel amplitude that can be used to improve the accuracy of the ordinary perturbative expansion of the Borel amplitude. In particular, we consider the Borel transform of the Adler function and its expansion around the first infrared renormalon due to the gluon condensate. Using the next-to-leading order (NLO) Wilson coefficient of the gluon condensate operator, we obtain an exact constraint on the Borel amplitude at the first IR renormalon. We then extrapolate, using judiciously chosen conformal transformations and Pade{prime} approximants, the ordinary perturbative expansion of the Borel amplitude in such a way that this constraint is satisfied. This procedure allows us to predict the O({alpha}{sub s}{sup 4}) coefficient of the Adler function, which gives a result consistent with the estimate by Kataev and Starshenko using a completely different method. We then apply this improved Borel amplitude to the tau decay width and obtain the strong coupling constant {alpha}{sub s}(M{sub z}{sup 2})=0.1193{+-}0.0007{sub exp.}{+-}0.0010{sub EW+CKM}{+-}0.0009{sub meth.}{+-}0.0003{sub evol.}. We then compare this result with those of other resummation methods.

  18. Axonal Transport Rates In Vivo Are Unaffected by Tau Deletion or Overexpression in Mice

    PubMed Central

    Yuan, Aidong; Kumar, Asok; Peterhoff, Corrinne; Duff, Karen; Nixon, Ralph A.

    2010-01-01

    Elevated tau expression has been proposed as a possible basis for impaired axonal transport in Alzheimer’s disease. To address this hypothesis, we analyzed the movement of pulse radiolabeled proteins in vivo along retinal ganglion cell (RGC) axons of mice that lack tau or overexpress human tau isoforms. Here, we show that the global axonal transport rates of slow and fast transport cargoes in axons are not significantly impaired when tau expression is eliminated or increased. In addition, markers of slow transport (neurofilament light subunit) and fast transport (snap25) do not accumulate in retinas and are distributed normally along optic axons in mice that lack or overexpress tau. Finally, ultrastructural analyses revealed no abnormal accumulations of vesicular organelles or neurofilaments in RGC perikarya or axons in mice overexpressing or lacking tau. These results suggest that tau is not essential for axonal transport and that transport rates in vivo are not significantly affected by substantial fluctuations in tau expression. PMID:18272688

  19. Observation of tau neutrino appearance in the CNGS beam with the OPERA experiment

    NASA Astrophysics Data System (ADS)

    Opera Collaboration; Agafonova, N.; Aleksandrov, A.; Anokhina, A.; Aoki, S.; Ariga, A.; Ariga, T.; Asada, T.; Bender, D.; Bertolin, A.; Bozza, C.; Brugnera, R.; Buonaura, A.; Buontempo, S.; Büttner, B.; Chernyavsky, M.; Chukanov, A.; Consiglio, L.; D'Ambrosio, N.; de Lellis, G.; de Serio, M.; Del Amo Sanchez, P.; di Crescenzo, A.; di Ferdinando, D.; di Marco, N.; Dmitrievski, S.; Dracos, M.; Duchesneau, D.; Dusini, S.; Dzhatdoev, T.; Ebert, J.; Ereditato, A.; Fini, R. A.; Fukuda, T.; Galati, G.; Garfagnini, A.; Giacomelli, G.; Goellnitz, C.; Goldberg, J.; Gornushkin, Y.; Grella, G.; Guler, M.; Gustavino, C.; Hagner, C.; Hara, T.; Hayakawa, T.; Hollnagel, A.; Hosseini, B.; Ishida, H.; Ishiguro, K.; Jakovcic, K.; Jollet, C.; Kamiscioglu, C.; Kamiscioglu, M.; Katsuragawa, T.; Kawada, J.; Kawahara, H.; Kim, J. H.; Kim, S. H.; Kitagawa, N.; Klicek, B.; Kodama, K.; Komatsu, M.; Kose, U.; Kreslo, I.; Lauria, A.; Lenkeit, J.; Ljubicic, A.; Longhin, A.; Loverre, P.; Malenica, M.; Malgin, A.; Mandrioli, G.; Matsuo, T.; Matveev, V.; Mauri, N.; Medinaceli, E.; Meregaglia, A.; Meyer, M.; Mikado, S.; Miyanishi, M.; Monacelli, P.; Montesi, M. C.; Morishima, K.; Muciaccia, M. T.; Naganawa, N.; Naka, T.; Nakamura, M.; Nakano, T.; Nakatsuka, Y.; Niwa, K.; Ogawa, S.; Okateva, N.; Olshevsky, A.; Omura, T.; Ozaki, K.; Paoloni, A.; Park, B. D.; Park, I. G.; Pasqualini, L.; Pastore, A.; Patrizii, L.; Pessard, H.; Pistillo, C.; Podgrudkov, D.; Polukhina, N.; Pozzato, M.; Pupilli, F.; Roda, M.; Roganova, T.; Rokujo, H.; Rosa, G.; Ryazhskaya, O.; Sato, O.; Schembri, A.; Shakiryanova, I.; Shchedrina, T.; Sheshukov, A.; Shibuya, H.; Shiraishi, T.; Shoziyoev, G.; Simone, S.; Sioli, M.; Sirignano, C.; Sirri, G.; Spinetti, M.; Stanco, L.; Starkov, N.; Stellacci, S. M.; Stipcevic, M.; Strolin, P.; Takahashi, S.; Tenti, M.; Terranova, F.; Tioukov, V.; Tufanli, S.; Umemoto, A.; Vilain, P.; Vladimirov, M.; Votano, L.; Vuilleumier, J. L.; Wilquet, G.; Wonsak, B.; Yoon, C. S.; Yaguchi, I.; Yoshimoto, M.; Zemskova, S.; Zghiche, A.

    2014-10-01

    The OPERA experiment is searching for ν _μ rArr ν _tau oscillations in appearance mode, i.e., via the direct detection of tau leptons in ν _tau charged-current interactions. The evidence of ν _μ rArr ν _tau appearance has been previously reported with three ν _tau candidate events using a sub-sample of data from the 2008-2012 runs. We report here a fourth ν _tau candidate event, with the tau decaying into a hadron, found after adding the 2012 run events without any muon in the final state to the data sample. Given the number of analyzed events and the low background, ν _μ rArr ν _tau oscillations are established with a significance of 4.2σ.

  20. Goodman and Kruskal's TAU-B Statistics: A Fortran-77 Subroutine.

    ERIC Educational Resources Information Center

    Berry, Kenneth J.; Mielke, Paul W., Jr.

    1986-01-01

    An algorithm and associated FORTRAN-77 computer subroutine are described for computing Goodman and Kruskal's tau-b statistic along with the associated nonasymptotic probability value under the null hypothesis tau=O. (Author)

  1. Depletion of microglia and inhibition of exosome synthesis halt tau propagation

    PubMed Central

    Asai, Hirohide; Ikezu, Seiko; Tsunoda, Satoshi; Medalla, Maria; Luebke, Jennifer; Haydar, Tarik; Wolozin, Benjamin; Butovsky, Oleg; Kügler, Sebastian; Ikezu, Tsuneya

    2015-01-01

    Accumulation of pathological tau protein is a major hallmark of Alzheimer’s disease. Tau protein spreads from the entorhinal cortex to the hippocampal region early in the disease. Microglia, the primary phagocytes in the brain, are positively correlated with tau pathology, but their involvement in tau propagation is unknown. We developed an adeno-associated virus–based model exhibiting rapid tau propagation from the entorhinal cortex to the dentate gyrus in 4 weeks. We found that depleting microglia dramatically suppressed the propagation of tau and reduced excitability in the dentate gyrus in this mouse model. Moreover, we demonstrate that microglia spread tau via exosome secretion, and inhibiting exosome synthesis significantly reduced tau propagation in vitro and in vivo. These data suggest that microglia and exosomes contribute to the progression of tauopathy and that the exosome secretion pathway may be a therapeutic target. PMID:26436904

  2. Microtubule-associated protein tau epitopes are present in fiber lesions in diverse muscle disorders.

    PubMed Central

    Lübke, U.; Six, J.; Villanova, M.; Boons, J.; Vandermeeren, M.; Ceuterick, C.; Cras, P.; Martin, J. J.

    1994-01-01

    The microtubule-associated protein tau is a major cytoskeletal protein involved in the neurofibrillary tangles of Alzheimer's disease. Although tau is predominantly a neuronal protein, it has been demonstrated in glia and other nonneuronal cells. We describe the presence of microtubule-associated protein tau epitopes in various muscle fiber lesions in oculopharyngeal and Becker muscular dystrophy, dermatomyositis, central core disease, neurogenic atrophy, and in the recovery phase of an attack of malignant hyperthermia. Western blot demonstrated a 100- to 110-kd tau-immunoreactive protein probably corresponding to 'big tau' as described in peripheral nerves. Tau immunoreactivity in muscle fiber lesions usually co-localized with tubulin, although electron microscopy failed to show an increase in microtubules. Tau and tubulin reactivity also correlated with the presence of desmin and vimentin epitopes. Possible explanations for the presence of tau are briefly discussed. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 PMID:7518193

  3. Measurements of the kaon content in tau decays

    SciTech Connect

    Ronan, M.T. )

    1992-02-01

    Results on measurements of the kaon content in one-prong and three-prong [tau] decays are presented for data taken by the TPC/2[gamma] detector at PEP. Using a self-consistent procedure to measure exclusive and inclusive decays, the one-prong analysis extends previous work to kaon decay modes. Three-prong results [ital K][pi][pi], [ital K][pi] and [ital KKK] decay modes provide improved branching ratios and a first look at strange axial-vector couplings in [tau] decays.

  4. The strong coupling from tau decays without prejudice

    NASA Astrophysics Data System (ADS)

    Boito, Diogo; Golterman, Maarten; Jamin, Matthias; Mahdavi, Andisheh; Maltman, Kim; Osborne, James; Peris, Santiago

    2014-08-01

    We review our recent determination of the strong coupling αs from the OPAL data for non-strange hadronic tau decays. We find that αs (mτ2)= 0.325 ± 0.018 using fixed-order perturbation theory, and αs (mτ2)= 0.347 ± 0.025 using contour-improved perturbation theory. At present, these values supersede any earlier determinations of the strong coupling from hadronic tau decays, including those from ALEPH data.

  5. Tau protein, the main component of paired helical filaments.

    PubMed

    Avila, Jesús

    2006-01-01

    In this volume we commemorate the centennial of Alois Alzheimer's discovery of what was later known as Alzheimer's disease, named by Alzheimer's mentor, Emil Kraepelin. In a much more low level, our group remember in this issue a paper published twenty years ago. In that paper it was described that tau can self-polymerize and, at that time, it suggested that tau was not only a component of Alzheimer paired helical filaments, as indicated some months earlier during that year, 1986, but that it was the main component of Alzheimer paired helical filaments.

  6. Studies of the Strange Hadronic Tau Decay Tau- to K0(S) Pi- Nu-Tau Using the BaBar Detector

    SciTech Connect

    Lyon, Andrew J.; /Manchester U. /SLAC

    2006-01-27

    A study of the decay {tau}{sup -} {yields} K{sub S}{sup 0}{pi}{sup -} {nu}{sub {tau}} (K{sub S}{sup 0} {yields} {pi}{sup +}{pi}{sup -}) using the BABAR detector is presented. Using 124.4 fb{sup -1} of data we measure {Beta}({tau}{sup -} {yields} {bar K}{sup 0}{pi}{sup -}{nu}{sub {tau}}) = (0.830 {+-} 0.005(stat) {+-} 0.042(syst))%, which is the world's most precise measurement to date of this branching ratio, and is consistent with the current world average. This preliminary result, unlike most of the {Beta}({tau}{sup -} {yields} {bar K}{sup 0}{pi}{sup -}{nu}{sub {tau}}) measurements already published, is systematics dominated and so the biggest future improvement to this number should come from reducing the systematic uncertainties in the analysis. A study of the K{pi} mass spectrum, from which the strange (K{pi}) spectral function can be measured, reveals excess contributions above the K*(892) tail at higher K{pi} mass. While in the past this has been thought to be due to K*(892) - K*(1410) interference, we find that the K*(1410), whose branching ratio to K{pi} is approximately 7%, seems insufficient to explain the excess mass observed in the data. Instead, we perform a fit using a K*(892) - K*(1680) interference model and find better agreement. The discrepancy that remains could be due to an s-wave contribution to the interference that is not parameterized in the model used, and/or detector smearing that is not accounted for in our fit. We also attempt to find an s-wave contribution to the K{pi} mass spectrum by searching for an sp-interference effect. While we find a hint that such an effect exists, we have neither the confidence in the statistics nor systematics in the higher K{pi} mass region to announce an observation. We conclude that it would be a worthwhile study to pursue.

  7. Measurement of the Absolute Branching Fraction of D{sub s}{sup +}{yields}{tau}{sup +}{nu}{sub {tau}} Decay

    SciTech Connect

    Ecklund, K. M.; Love, W.; Savinov, V.; Lopez, A.; Mendez, H.; Ramirez, J.; Ge, J. Y.; Miller, D. H.; Shipsey, I. P. J.; Xin, B.; Adams, G. S.; Anderson, M.; Cummings, J. P.; Danko, I.; Hu, D.; Moziak, B.; Napolitano, J.; He, Q.; Insler, J.; Muramatsu, H.

    2008-04-25

    Using a sample of tagged D{sub s}{sup +} decays collected near the D{sub s}*{sup {+-}}D{sub s}{sup {+-}} peak production energy in e{sup +}e{sup -} collisions with the CLEO-c detector, we study the leptonic decay D{sub s}{sup +}{yields}{tau}{sup +}{nu}{sub {tau}} via the decay channel {tau}{sup +}{yields}e{sup +}{nu}{sub e}{nu}{sub {tau}}. We measure B(D{sub s}{sup +}{yields}{tau}{sup +}{nu}{sub {tau}})=(6.17{+-}0.71{+-}0.34)%, where the first error is statistical and the second systematic. Combining this result with our measurements of D{sub s}{sup +}{yields}{mu}{sup +}{nu}{sub {mu}} and D{sub s}{sup +}{yields}{tau}{sup +}{nu}{sub {tau}} (via {tau}{sup +}{yields}{pi}{sup +}{nu}{sub {tau}}), we determine f{sub D{sub s}}=(274{+-}10{+-}5) MeV.

  8. Insulin resistance is associated with higher cerebrospinal fluid tau levels in asymptomatic APOE ε4 carriers

    PubMed Central

    Starks, Erika J.; O'Grady, J. Patrick; Hoscheidt, Siobhan M.; Racine, Annie M.; Carlsson, Cindy M.; Zetterberg, Henrik; Blennow, Kaj; Okonkwo, Ozioma C.; Puglielli, Luigi; Asthana, Sanjay; Dowling, N. Maritza; Gleason, Carey E.; Anderson, Rozalyn M.; Davenport-Sis, Nancy J.; DeRungs, LeAnn M.; Sager, Mark A.; Johnson, Sterling C.; Bendlin, Barbara B.

    2015-01-01

    Background Insulin resistance (IR) is linked with the occurrence of pathological features observed in Alzheimer's disease (AD), including neurofibrillary tangles and amyloid plaques. However, the extent to which IR is associated with AD pathology in the cognitively asymptomatic stages of preclinical AD remains unclear. Objective To determine the extent to which IR is linked with amyloid and tau pathology in late-middle-age. Method Cerebrospinal fluid (CSF) samples collected from 113 participants enrolled in the Wisconsin Registry for Alzheimer's Prevention study (mean age = 60.6 years), were assayed for AD-related markers of interest: Aβ42, P-Tau181, and T-Tau. IR was determined using the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). Linear regression was used to test the effect of IR, and APOE ε4, on tau and amyloid pathology. We hypothesized that greater IR would be associated with higher CSF P-Tau181 and T-Tau, and lower CSF Aβ42. Results No significant main effects of HOMA-IR on P-Tau181, T-Tau, or Aβ42 were observed; however, significant interactions were observed between HOMA-IR and APOE ε4 on CSF markers related to tau. Among APOE ε4 carriers, higher HOMA-IR was associated with higher P-Tau181 and T-Tau. Among APOE ε4 non-carriers, HOMA-IR was negatively associated with P-Tau181 and T-Tau. We found no effects of IR on Aβ42 levels in CSF. Conclusion IR among asymptomatic APOE ε4 carriers was associated with higher P-Tau181 and T-Tau in late-middle age. The results suggest that IR may contribute to tau-related neurodegeneration in preclinical AD. The findings may have implications for developing prevention strategies aimed at modifying IR in mid-life. PMID:25812851

  9. Validation of ELISA methods for quantification of total tau and phosporylated-tau181 in human cerebrospinal fluid with measurement in specimens from two Alzheimer's disease studies.

    PubMed

    Lachno, D Richard; Romeo, Martin J; Siemers, Eric R; Vanderstichele, Hugo; Coart, Els; Konrad, Robert J; Zajac, Joseph J; Talbot, Jayne A; Jensen, Hans F; Sethuraman, Gopalan; Demattos, Ronald B; May, Patrick C; Dean, Robert A

    2011-01-01

    Tau measurements in cerebrospinal fluid (CSF) are gaining acceptance as aids to diagnosis of Alzheimer's disease (AD) and differentiation from other dementias. Two ELISA assays, the INNOTEST® hTAU Ag and the INNOTEST® PHOSPHO-TAU(181P) for quantification of t-tau and p-tau181 respectively, have been validated to regulatory standards. Validation parameters were determined by repeated testing of human CSF pools. Specimens from Phase 2 studies of the γ-secretase inhibitor semagacestat and the therapeutic antibody solanezumab at baseline and following 12-14 weeks of treatment were also tested. Estimated intra-assay CV for repeated testing of 3 CSF pools were ≤11.5% and RE varied between -14.1% and +6.4%. Inter-assay CV for t-tau was <5% and RE was within ±8%. For p-tau181, inter-assay CV was <9% and RE was within ±2.5%. Total CV (intra-assay plus inter-assay) were below 10% for both analytes. Up to 20-fold dilutional linearity was demonstrated for both analytes. Stability of t-tau and p-tau181 was demonstrated in CSF during five freeze-thaw cycles at ≤-20 °C and ≤-70 °C and at 18-22 °C for up to 24 h. Neither semagacestat nor solanezumab interfered with either assay. Inter-individual t-tau and p-tau181 concentrations were highly variable but intra-individual variations were small. These assays are suitable for analysis of CSF t-tau and p-tau181 in a single laboratory supporting multi-center AD clinical trials. No effect of treatment with semagacestat or solanezumab was observed in response to three months of drug administration. PMID:21694458

  10. Ab initio alpha-alpha scattering.

    PubMed

    Elhatisari, Serdar; Lee, Dean; Rupak, Gautam; Epelbaum, Evgeny; Krebs, Hermann; Lähde, Timo A; Luu, Thomas; Meißner, Ulf-G

    2015-12-01

    Processes such as the scattering of alpha particles ((4)He), the triple-alpha reaction, and alpha capture play a major role in stellar nucleosynthesis. In particular, alpha capture on carbon determines the ratio of carbon to oxygen during helium burning, and affects subsequent carbon, neon, oxygen, and silicon burning stages. It also substantially affects models of thermonuclear type Ia supernovae, owing to carbon detonation in accreting carbon-oxygen white-dwarf stars. In these reactions, the accurate calculation of the elastic scattering of alpha particles and alpha-like nuclei--nuclei with even and equal numbers of protons and neutrons--is important for understanding background and resonant scattering contributions. First-principles calculations of processes involving alpha particles and alpha-like nuclei have so far been impractical, owing to the exponential growth of the number of computational operations with the number of particles. Here we describe an ab initio calculation of alpha-alpha scattering that uses lattice Monte Carlo simulations. We use lattice effective field theory to describe the low-energy interactions of protons and neutrons, and apply a technique called the 'adiabatic projection method' to reduce the eight-body system to a two-cluster system. We take advantage of the computational efficiency and the more favourable scaling with system size of auxiliary-field Monte Carlo simulations to compute an ab initio effective Hamiltonian for the two clusters. We find promising agreement between lattice results and experimental phase shifts for s-wave and d-wave scattering. The approximately quadratic scaling of computational operations with particle number suggests that it should be possible to compute alpha scattering and capture on carbon and oxygen in the near future. The methods described here can be applied to ultracold atomic few-body systems as well as to hadronic systems using lattice quantum chromodynamics to describe the interactions of

  11. Ab initio alpha-alpha scattering.

    PubMed

    Elhatisari, Serdar; Lee, Dean; Rupak, Gautam; Epelbaum, Evgeny; Krebs, Hermann; Lähde, Timo A; Luu, Thomas; Meißner, Ulf-G

    2015-12-01

    Processes such as the scattering of alpha particles ((4)He), the triple-alpha reaction, and alpha capture play a major role in stellar nucleosynthesis. In particular, alpha capture on carbon determines the ratio of carbon to oxygen during helium burning, and affects subsequent carbon, neon, oxygen, and silicon burning stages. It also substantially affects models of thermonuclear type Ia supernovae, owing to carbon detonation in accreting carbon-oxygen white-dwarf stars. In these reactions, the accurate calculation of the elastic scattering of alpha particles and alpha-like nuclei--nuclei with even and equal numbers of protons and neutrons--is important for understanding background and resonant scattering contributions. First-principles calculations of processes involving alpha particles and alpha-like nuclei have so far been impractical, owing to the exponential growth of the number of computational operations with the number of particles. Here we describe an ab initio calculation of alpha-alpha scattering that uses lattice Monte Carlo simulations. We use lattice effective field theory to describe the low-energy interactions of protons and neutrons, and apply a technique called the 'adiabatic projection method' to reduce the eight-body system to a two-cluster system. We take advantage of the computational efficiency and the more favourable scaling with system size of auxiliary-field Monte Carlo simulations to compute an ab initio effective Hamiltonian for the two clusters. We find promising agreement between lattice results and experimental phase shifts for s-wave and d-wave scattering. The approximately quadratic scaling of computational operations with particle number suggests that it should be possible to compute alpha scattering and capture on carbon and oxygen in the near future. The methods described here can be applied to ultracold atomic few-body systems as well as to hadronic systems using lattice quantum chromodynamics to describe the interactions of

  12. Is phosphorylated tau unique to chronic traumatic encephalopathy? Phosphorylated tau in epileptic brain and chronic traumatic encephalopathy.

    PubMed

    Puvenna, Vikram; Engeler, Madeline; Banjara, Manoj; Brennan, Chanda; Schreiber, Peter; Dadas, Aaron; Bahrami, Ashkon; Solanki, Jesal; Bandyopadhyay, Anasua; Morris, Jacqueline K; Bernick, Charles; Ghosh, Chaitali; Rapp, Edward; Bazarian, Jeffrey J; Janigro, Damir

    2016-01-01

    Repetitive traumatic brain injury (rTBI) is one of the major risk factors for the abnormal deposition of phosphorylated tau (PT) in the brain and chronic traumatic encephalopathy (CTE). CTE and temporal lobe epilepsy (TLE) affect the limbic system, but no comparative studies on PT distribution in TLE and CTE are available. It is also unclear whether PT pathology results from repeated head hits (rTBI). These gaps prevent a thorough understanding of the pathogenesis and clinical significance of PT, limiting our ability to develop preventative and therapeutic interventions. We quantified PT in TLE and CTE to unveil whether a history of rTBI is a prerequisite for PT accumulation in the brain. Six postmortem CTE (mean 73.3 years) and age matched control samples were compared to 19 surgically resected TLE brain specimens (4 months-58 years; mean 27.6 years). No history of TBI was present in TLE or control; all CTE patients had a history of rTBI. TLE and CTE brain displayed increased levels of PT as revealed by immunohistochemistry. No age-dependent changes were noted, as PT was present as early as 4 months after birth. In TLE and CTE, cortical neurons, perivascular regions around penetrating pial vessels and meninges were immunopositive for PT; white matter tracts also displayed robust expression of extracellular PT organized in bundles parallel to venules. Microscopically, there were extensive tau-immunoreactive neuronal, astrocytic and degenerating neurites throughout the brain. In CTE perivascular tangles were most prominent. Overall, significant differences in staining intensities were found between CTE and control (P<0.01) but not between CTE and TLE (P=0.08). pS199 tau analysis showed that CTE had the most high molecular weight tangle-associated tau, whereas epileptic brain contained low molecular weight tau. Tau deposition may not be specific to rTBI since TLE recapitulated most of the pathological features of CTE. PMID:26556772

  13. Rapamycin ester analog CCI-779/Temsirolimus alleviates tau pathology and improves motor deficit in mutant tau transgenic mice.

    PubMed

    Frederick, Christelle; Ando, Kunie; Leroy, Karelle; Héraud, Céline; Suain, Valérie; Buée, Luc; Brion, Jean-Pierre

    2015-01-01

    Neurofibrillary tangles are intracellular inclusions made of tau protein that accumulates in neurons in Alzheimer's disease (AD) and in other tauopathies. We have investigated the ability of the rapamycin ester CCI-779/Temsilorimus, a mTOR inhibitor with better stability and pharmacological properties compared to rapamycin, to interfere with the development of a motor phenotype and tau pathology in a mutant tau mouse model developing neurofibrillary tangles, by stimulation of mTOR dependent macroautophagy. Mutant tau mice (Tg30) were treated with CCI-779 before onset of motor signs for 7 months (from 5 to 12 months of age) or after the onset of motor signs for 2 months (from 10 to 12 months of age). End-point motor deficits were 50% lower in the group of Tg30 mice treated for 7 months. Inhibition of mTOR signaling and stimulation of macroautophagy in the brain of CCI-779 treated Tg30 mice was suggested by decreased phosphorylation of mTOR downstream signaling molecules p70S6 kinase and Akt and increased level of the autophagy markers Rab7 and LC3-II. CCI-779 treatment decreased the brain levels of Sarkosyl-insoluble tau and phosphotau inTg30 mice both after 2 months or 7 months of treatment. The density of neurofibrillary tangles was significantly decreased when treatment was started prior onset of motor signs. These results indicate that stimulation of mTOR dependent autophagy by CCI-779 compound is efficient to counteract the accumulation of abnormal tau when administered early or late in a tauopathy model and to improve a motor deficit when started before onset of motor signs.

  14. Is phosphorylated tau unique to chronic traumatic encephalopathy? Phosphorylated tau in epileptic brain and chronic traumatic encephalopathy.

    PubMed

    Puvenna, Vikram; Engeler, Madeline; Banjara, Manoj; Brennan, Chanda; Schreiber, Peter; Dadas, Aaron; Bahrami, Ashkon; Solanki, Jesal; Bandyopadhyay, Anasua; Morris, Jacqueline K; Bernick, Charles; Ghosh, Chaitali; Rapp, Edward; Bazarian, Jeffrey J; Janigro, Damir

    2016-01-01

    Repetitive traumatic brain injury (rTBI) is one of the major risk factors for the abnormal deposition of phosphorylated tau (PT) in the brain and chronic traumatic encephalopathy (CTE). CTE and temporal lobe epilepsy (TLE) affect the limbic system, but no comparative studies on PT distribution in TLE and CTE are available. It is also unclear whether PT pathology results from repeated head hits (rTBI). These gaps prevent a thorough understanding of the pathogenesis and clinical significance of PT, limiting our ability to develop preventative and therapeutic interventions. We quantified PT in TLE and CTE to unveil whether a history of rTBI is a prerequisite for PT accumulation in the brain. Six postmortem CTE (mean 73.3 years) and age matched control samples were compared to 19 surgically resected TLE brain specimens (4 months-58 years; mean 27.6 years). No history of TBI was present in TLE or control; all CTE patients had a history of rTBI. TLE and CTE brain displayed increased levels of PT as revealed by immunohistochemistry. No age-dependent changes were noted, as PT was present as early as 4 months after birth. In TLE and CTE, cortical neurons, perivascular regions around penetrating pial vessels and meninges were immunopositive for PT; white matter tracts also displayed robust expression of extracellular PT organized in bundles parallel to venules. Microscopically, there were extensive tau-immunoreactive neuronal, astrocytic and degenerating neurites throughout the brain. In CTE perivascular tangles were most prominent. Overall, significant differences in staining intensities were found between CTE and control (P<0.01) but not between CTE and TLE (P=0.08). pS199 tau analysis showed that CTE had the most high molecular weight tangle-associated tau, whereas epileptic brain contained low molecular weight tau. Tau deposition may not be specific to rTBI since TLE recapitulated most of the pathological features of CTE.

  15. Large Sample Confidence Limits for Goodman and Kruskal's Proportional Prediction Measure TAU-b

    ERIC Educational Resources Information Center

    Berry, Kenneth J.; Mielke, Paul W.

    1976-01-01

    A Fortran Extended program which computes Goodman and Kruskal's Tau-b, its asymmetrical counterpart, Tau-a, and three sets of confidence limits for each coefficient under full multinomial and proportional stratified sampling is presented. A correction of an error in the calculation of the large sample standard error of Tau-b is discussed.…

  16. 40 CFR 180.427 - Tau-Fluvalinate; tolerances for residues.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 24 2014-07-01 2014-07-01 false Tau-Fluvalinate; tolerances for... § 180.427 Tau-Fluvalinate; tolerances for residues. (a) General. Tolerances are established for residues of the insecticide tau-fluvalinate, cyano-(3-phenoxyphenyl)methyl N- -D-valinate, in or on...

  17. 40 CFR 180.427 - Tau-Fluvalinate; tolerances for residues.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Tau-Fluvalinate; tolerances for... § 180.427 Tau-Fluvalinate; tolerances for residues. (a) General. Tolerances are established for residues of the insecticide tau-fluvalinate, cyano-(3-phenoxyphenyl)methyl N- -D-valinate, in or on...

  18. 40 CFR 180.427 - Tau-Fluvalinate; tolerances for residues.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 25 2013-07-01 2013-07-01 false Tau-Fluvalinate; tolerances for... § 180.427 Tau-Fluvalinate; tolerances for residues. (a) General. Tolerances are established for residues of the insecticide tau-fluvalinate, cyano-(3-phenoxyphenyl)methyl N- -D-valinate, in or on...

  19. 40 CFR 180.427 - Tau-Fluvalinate; tolerances for residues.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 25 2012-07-01 2012-07-01 false Tau-Fluvalinate; tolerances for... § 180.427 Tau-Fluvalinate; tolerances for residues. (a) General. Tolerances are established for residues of the insecticide tau-fluvalinate, cyano-(3-phenoxyphenyl)methyl N- -D-valinate, in or on...

  20. 40 CFR 180.427 - Tau-Fluvalinate; tolerances for residues.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Tau-Fluvalinate; tolerances for... § 180.427 Tau-Fluvalinate; tolerances for residues. (a) General. Tolerances are established for residues of the insecticide tau-fluvalinate, cyano-(3-phenoxyphenyl)methyl N- -D-valinate, in or on...

  1. Learning and Memory Deficits upon TAU Accumulation in "Drosophila" Mushroom Body Neurons

    ERIC Educational Resources Information Center

    Mershin, Andreas; Pavlopoulos, Elias; Fitch, Olivia; Braden, Brittany C.; Nanopoulos, Dimitri V.; Skoulakis, Efthimios M. C.

    2004-01-01

    Mutations in the neuronal-specific microtubule-binding protein TAU are associated with several dementias and neurodegenerative diseases. However, the effects of elevated TAU accumulation on behavioral plasticity are unknown. We report that directed expression of wild-type vertebrate and "Drosophila" TAU in adult mushroom body neurons, centers for…

  2. Argyrophilic grain disease differs from other tauopathies by lacking tau acetylation

    PubMed Central

    Grinberg, Lea Tenenholz; Wang, Xuehua; Wang, Chao; Sohn, Peter Dongmin; Theofilas, Panos; Sidhu, Manu; Arevalo, John Benjamin; Heinsen, Helmut; Huang, Eric J.; Rosen, Howard; Miller, Bruce L.; Gan, Li; Seeley, William W.

    2013-01-01

    Post-translational modifications play a key role in tau protein aggregation and related neurodegeneration. Because hyperphosphorylation alone does not necessarily cause tau aggregation, other post-translational modifications have been recently explored. Tau acetylation promotes aggregation and inhibits tau’s ability to stabilize microtubules. Recent studies have shown co-localization of acetylated and phosphorylated tau in AD and some 4R tauopathies. We developed a novel monoclonal antibody against acetylated tau at lysine residue 274, which recognizes both 3R and 4R tau, and used immunohistochemistry and immunofluorescence to probe 22 cases, including AD and another eight familial or sporadic tauopathies. Acetylated tau was identified in all tauopathies except argyrophilic grain disease (AGD). AGD is an age-associated, common but atypical 4R tauopathy, not always associated with clinical progression. Pathologically, AGD is characterized by neuropil grains, pre-neurofibrillary tangles, and oligodendroglial coiled bodies, all recognized by phospho-tau antibodies. The lack of acetylated tau in these inclusions suggests that AGD represents a distinctive tauopathy. Our data converge with previous findings to raise the hypothesis that AGD could play a protective role against the spread of AD-related tau pathology. Tau acetylation as a key modification for the propagation tau toxicity deserves further investigation. PMID:23371364

  3. Convergence of Presenilin- and Tau-mediated Pathways on Axonal Trafficking and Neuronal Function

    PubMed Central

    Peethumnongsin, Erica; Yang, Li; Kallhoff-Muñoz, Verena; Hu, Lingyun; Takashima, Akihiko; Pautler, Robia G.; Zheng, Hui

    2010-01-01

    Alzheimer’s disease (AD) is a significant and growing health problem in the aging population. Although definitive mechanisms of pathogenesis remain elusive, genetic and histological clues have implicated the proteins presenilin (PS) and tau as key players in AD development. PS mutations lead to familial AD, and although tau is not mutated in AD, tau pathology is a hallmark of the disease. Axonal transport deficits are a common feature of several neurodegenerative disorders and may represent a point of intersection of PS and tau function. To investigate the contribution of wild-type, as opposed to mutant, tau to axonal transport defects in the context of presenilin loss, we used a mouse model postnatally deficient for PS (PS cDKO) and expressing wild-type human tau (WtTau). The resulting PS cDKO;WtTau mice exhibited early tau pathology and axonal transport deficits that preceded development of these phenotypes in WtTau or PS cDKO mice. These deficits were associated with reduced neurotrophin signaling, defective learning and memory and impaired synaptic plasticity. The combination of these effects accelerated neurodegeneration in PS cDKO;WtTau mice. Our results strongly support a convergent role for PS and tau in axonal transport and neuronal survival and function and implicate their misregulation as a contributor to AD pathogenesis. PMID:20926667

  4. A novel calcium-binding protein is associated with tau proteins in tauopathy

    PubMed Central

    Vega, Irving E.; Traverso, Edwin E.; Ferrer-Acosta, Yancy; Matos, Eduardo; Colon, Migdalisel; Gonzalez, John; Dickson, Dennis; Hutton, Michael; Lewis, Jada; Yen, Shu H.

    2013-01-01

    Tauopathies are a group of neurological disorders characterized by the presence of intraneuronal hyperphosphorylated and filamentous tau. Mutations in the tau gene have been found in kindred with tauopathy. The expression of the human tau mutant in transgenic mice induced neurodegeneration, indicating that tau plays a central pathological role. However, the molecular mechanism leading to tau-mediated neurodegeneration is poorly understood. To gain insights into the role that tau plays in neurodegeneration, human tau proteins were immunoprecipitated from brain lysates of the tauopathy mouse model JNPL3, which develops neurodegeneration in age-dependent manner. In the present work, a novel EF-hand domain-containing protein was found associated with tau proteins in brain lysate of 12-month-old JNPL3 mice. The association between tau proteins and the novel identified protein appears to be induced by the neurodegeneration process as these two proteins were not found associated in young JNPL3 mice. Consistently, the novel protein co-purified with the pathological sarkosyl insoluble tau in terminally ill JNPL3 mice. Calcium-binding assays demonstrated that this protein binds calcium effectively. Finally, the association between tau and the novel calcium-binding protein is conserved in human and enriched in Alzheimer's disease brain. Taken together, the identification of a novel calcium-binding protein associated with tau protein in terminally ill tauopathy mouse model and its confirmation in human brain lysate suggests that this association may play an important physiological and/or pathological role. PMID:18346207

  5. Abnormal tau induces cognitive impairment through two different mechanisms: synaptic dysfunction and neuronal loss

    PubMed Central

    Di, J.; Cohen, L. S.; Corbo, C. P.; Phillips, G. R.; El Idrissi, A.; Alonso, A. D.

    2016-01-01

    The hyperphosphorylated microtubule-associated protein tau is present in several neurodegenerative diseases, although the causal relationship remains elusive. Few mouse models used to study Alzheimer-like dementia target tau phosphorylation. We created an inducible pseudophosphorylated tau (Pathological Human Tau, PH-Tau) mouse model to study the effect of conformationally modified tau in vivo. Leaky expression resulted in two levels of PH-Tau: low basal level and higher upon induction (4% and 14% of the endogenous tau, respectively). Unexpectedly, low PH-Tau resulted in significant cognitive deficits, decrease in the number of synapses (seen by EM in the CA1 region), reduction of synaptic proteins, and localization to the nucleus. Induction of PH-Tau triggered neuronal death (60% in CA3), astrocytosis, and loss of the processes in CA1. These findings suggest, that phosphorylated tau is sufficient to induce neurodegeneration and that two different mechanisms can induce cognitive impairment depending on the levels of PH-Tau expression. PMID:26888634

  6. The Role of Tau in Neurodegenerative Diseases and Its Potential as a Therapeutic Target

    PubMed Central

    2012-01-01

    The abnormal deposition of proteins in and around neurons is a common pathological feature of many neurodegenerative diseases. Among these pathological proteins, the microtubule-associated protein tau forms intraneuronal filaments in a spectrum of neurological disorders. The discovery that dominant mutations in the MAPT gene encoding tau are associated with familial frontotemporal dementia strongly supports abnormal tau protein as directly involved in disease pathogenesis. This and other evidence suggest that tau is a worthwhile target for the prevention or treatment of tau-associated neurodegenerative diseases, collectively called tauopathies. However, it is critical to understand the normal biological roles of tau, the specific molecular events that induce tau to become neurotoxic, the biochemical nature of pathogenic tau, the means by which pathogenic tau exerts neurotoxicity, and how tau pathology propagates. Based on known differences between normal and abnormal tau, a number of approaches have been taken toward the discovery of potential therapeutics. Key questions still remain open, such as the nature of the connection between the amyloid-β protein of Alzheimer's disease and tau pathology. Answers to these questions should help better understand the nature of tauopathies and may also reveal new therapeutic targets and strategies. PMID:24278740

  7. alpha-Hexachlorocyclohexane (alpha-HCH)

    Integrated Risk Information System (IRIS)

    alpha - Hexachlorocyclohexane ( alpha - HCH ) ; CASRN 319 - 84 - 6 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Ass

  8. H{alpha} ABSORPTION IN TRANSITING EXOPLANET ATMOSPHERES

    SciTech Connect

    Christie, Duncan; Arras, Phil; Li Zhiyun E-mail: pla7y@virginia.edu

    2013-08-01

    Absorption of stellar H{alpha} by the upper atmosphere of the planet HD 189733b has recently been detected by Jensen et al. Motivated by this observation, we have developed a model for atomic hydrogen in the n = 2 state and compared the resulting H{alpha} line profile to the observations. The model atmosphere is in hydrostatic balance, as well as thermal and photoionization equilibrium. Collisional and radiative transitions are included in the determination of the n = 2 state level population. We find that H{alpha} absorption is dominated by an optical depth {tau} {approx} 1 shell, composed of hydrogen in the metastable 2s state that is located below the hydrogen ionization layer. The number density of the 2s state within the shell is found to vary slowly with radius, while that of the 1s state falls rapidly. Thus while the Ly{alpha} absorption, for a certain wavelength, occurs inside a relatively well defined impact parameter, the contribution to H{alpha} absorption is roughly uniform over the entire atomic hydrogen layer. The model can approximately reproduce the observed Ly{alpha} and H{alpha} integrated transit depths for HD 189733b by using an ionization rate enhanced over that expected for the star by an order of magnitude. For HD 209458b, we are unable to explain the asymmetric H{alpha} line profile observed by Jensen et al., as the model produces a symmetric line profile with transit depth comparable to that of HD 189733b. In an appendix, we study the effect of the stellar Ly{alpha} absorption on the net cooling rate.

  9. Reconstruction and classification of tau lepton decays with ILD

    NASA Astrophysics Data System (ADS)

    Tran, T. H.; Balagura, V.; Boudry, V.; Brient, J.-C.; Videau, H.

    2016-08-01

    Tau lepton decays with up to two π ^0s in the final state - τ ^+ → π ^+ bar{ν }_τ , ρ ^+ (π ^+π ^0) bar{ν }_τ , and {a}1+(π ^+π ^0π ^0) bar{ν }_τ - are used to study the performance of the barrel region of the silicon-tungsten electromagnetic calorimeter (Si-W ECAL) of the International Large Detector (ILD) at the future e+ e- International Linear Collider. Correct reconstruction of the tau decay mode is crucial for constraining the spin state of tau lepton and measuring the Higgs boson CP state in H{}{} → τ ^+τ ^- decays. We find that about 95 % of π ^+ bar{ν }_τ , and 90 % of ρ ^+bar{ν }_τ and {a}1+bar{ν }_τ decays produced by the e+ e- → {Z0}^*→ τ ^+τ ^- process at an e^± beam energy of 125 GeV are correctly reconstructed. In a smaller ILD detector, with the inner Si-W ECAL radius reduced by about 20 %, these efficiencies are reduced by at most 2 %. The π ^0 mass resolution remains below 10 %. Since failures in tau lepton reconstruction are mainly due to photons, an increase of the ILD magnetic field from 3.5 to 4 T does not bring any significant improvement.

  10. Secondary nucleating sequences affect kinetics and thermodynamics of tau aggregation.

    PubMed

    Moore, Christopher L; Huang, Michael H; Robbennolt, Shauna A; Voss, Kellen R; Combs, Benjamin; Gamblin, T Chris; Goux, Warren J

    2011-12-20

    Tau protein was scanned for highly amyloidogenic sequences in amphiphilic motifs (X)(n)Z, Z(X)(n)Z (n ≥ 2), or (XZ)(n) (n ≥ 2), where X is a hydrophobic residue and Z is a charged or polar residue. N-Acetyl peptides homologous to these sequences were used to study aggregation. Transmission electron microscopy (TEM) showed seven peptides, in addition to well-known primary nucleating sequences Ac(275)VQIINK (AcPHF6*) and Ac(306)VQIVYK (AcPHF6), formed fibers, tubes, ribbons, or rolled sheets. Of the peptides shown by TEM to form amyloid, Ac(10)VME, AcPHF6*, Ac(375)KLTFR, and Ac(393)VYK were found to enhance the fraction of β-structure of AcPHF6 formed at equilibrium, and Ac(375)KLTFR was found to inhibit AcPHF6 and AcPHF6* aggregation kinetics in a dose-dependent manner, consistent with its participation in a hybrid steric zipper model. Single site mutants were generated which transformed predicted amyloidogenic sequences in tau into non-amyloidogenic ones. A M11K mutant had fewer filaments and showed a decrease in aggregation kinetics and an increased lag time compared to wild-type tau, while a F378K mutant showed significantly more filaments. Our results infer that sequences throughout tau, in addition to PHF6 and PHF6*, can seed amyloid formation or affect aggregation kinetics or thermodynamics.

  11. Aggregation propensity of critical regions of the protein Tau

    NASA Astrophysics Data System (ADS)

    Muthee, Micaiah; Ahmed, Azka; Larini, Luca

    The Alzheimer's disease is an irreversible, progressive brain disorder that slowly destroys memory and thinking skills, which eventually leads to the ability to not able to carry out the simplest tasks. The Alzheimer's disease is characterized by the formation of protein aggregates both within and outside of the brain's cells, the neurons. Within the neurons, the aggregation of the protein tau leads to the destruction of the microtubules in the axon of the neuron. Tau belongs to a group of proteins referred to as Microtubule-Associated Proteins. It is extremely flexible and is classified as an intrinsically unstructured protein due to its low propensity to form secondary structure. Tau promotes tubulin assembly into microtubules thereby stabilizing the cytoskeleton of the axon of the neurons. The microtubule binding region of tau consists of 4 pseudo-repeats. In this study, we will focus on the aggregation propensity of two fragments. In this study we will focus on the PHF43 fragment that contains the third pseudo-repeat and has been shown experimentally to aggregate readily. Another fragment that contains the second pseudo-repeat will be considered as well. Mutations in this region are associated with various form of dementia and for this reason we will consider the mutant P301L.

  12. Detection of tau neutrinos by imaging air Cherenkov telescopes

    NASA Astrophysics Data System (ADS)

    Góra, D.; Bernardini, E.

    2016-09-01

    This paper investigates the potential to detect tau neutrinos in the energy range of 1-1000 PeV searching for very inclined showers with imaging Cherenkov telescopes. A neutrino induced tau lepton escaping from the Earth may decay and initiate an air shower which can be detected by a fluorescence or Cherenkov telescope. We present here a study of the detection potential of Earth-skimming neutrinos taking into account neutrino interactions in the Earth crust, local matter distributions at various detector sites, the development of tau-induced showers in air and the detection of Cherenkov photons with IACTs. We analyzed simulated shower images on the camera focal plane and implemented generic reconstruction chains based on Hillas parameters. We find that present IACTs can distinguish air showers induced by tau neutrinos from the background of hadronic showers in the PeV-EeV energy range. We present the neutrino trigger efficiency obtained for a few configurations being considered for the next-generation Cherenkov telescopes, i.e. the Cherenkov Telescope Array. Finally, for a few representative neutrino spectra expected from astrophysical sources, we compare the expected event rates at running IACTs to what is expected for the dedicated IceCube neutrino telescope.

  13. Multinomial Tau-Leaping Method for Stochastic Kinetic Simulations

    SciTech Connect

    Pettigrew, Michel F.; Resat, Haluk

    2007-02-28

    We introduce the multinomial tau-leaping (MtL) method, an improved version of the binomial tau-leaping method, for general reaction networks. Improvements in efficiency are achieved in several ways. Firstly, tau-leaping steps are determined simply and efficiently using a-prior information. Secondly, networks are partitioned into closed groups of reactions and corresponding reactants in which no group reactant or reaction is found in any other group. Thirdly, product formation is factored into upper bound estimation of the number of times a particular reaction occurs. Together, these features allow for larger time steps where the numbers of reactions occurring simultaneously in a multi-channel manner are estimated accurately using a multinomial distribution. Using a wide range of test case problems of scientific and practical interest involving cellular processes, such as epidermal growth factor receptor signaling and lactose operon model incorporating gene transcription and translation, we show that tau-leaping based methods like the MtL algorithm can significantly reduce the number of simulation steps thus increasing the numerical efficiency over the exact stochastic simulation algorithm by orders of magnitude. Furthermore, the simultaneous multi-channel representation capability of the MtL algorithm makes it a candidate for FPGA implementation or for parallelization in parallel computing environments.

  14. Ordered Binary Trees Constructed Through an Application of Kendall's Tau.

    ERIC Educational Resources Information Center

    Degerman, Richard

    1982-01-01

    A procedure is described for orienting the nodes of a binary tree to maximize the Kendall rank order correlation (tau) between node order and a given external criterion. The procedure is computationally efficient and is based on application of an ordered set of node tests. (Author)

  15. Evaluation of a multiplex PCR for detection of serotypes K1, K2 and K5 in Klebsiella sp. and comparison of isolates within these serotypes.

    PubMed

    Turton, Jane F; Baklan, Hatice; Siu, L K; Kaufmann, Mary E; Pitt, Tyrone L

    2008-07-01

    A multiplex PCR using targets within the serotype-specific region of the capsular polysaccharide synthesis gene cluster of serotypes K1, K2 and K5 was evaluated using the 77 reference serotype strains of Klebsiella, and a panel of clinical isolates subjected previously to conventional serotyping. The PCR was highly specific for these serotypes, which are those most associated with virulence in humans and horses. PCR confirmed that isolates of the K5 serotype had cross-reacted with antiserum for other serotypes, particularly for K7. K5 isolates received by our laboratory were almost exclusively from thoroughbred horses, and were submitted for screening prior to breeding programmes. Most, including a reference strain isolated in 1955, belonged to a cluster of genetically similar isolates of sequence type (ST) 60. K1 isolates, all from humans, belonged to a previously identified cluster of ST 23.

  16. Effects of the tropical ginger compound,1’-acetoxychavicol acetate, against tumor promotion in K5.Stat3C transgenic mice

    PubMed Central

    2012-01-01

    The purpose of the current study was to determine whether a tropical ginger derived compound 1’-acetoxychavicol acetate (ACA), suppresses skin tumor promotion in K5.Stat3C mice. In a two-week study in which wild-type (WT) and K5.Stat3C mice were co-treated with either vehicle, ACA, galanga extract, or fluocinolone acetonide (FA) and tetradecanoyl phorbol acetate (TPA), only the galanga extract and FA suppressed TPA-induced skin hyperproliferation and wet weight. None of these agents were effective at suppressing p-Tyr705Stat3 expression. However, ACA and FA showed promising inhibitory effects against skin tumorigenesis in K5.Stat3C mice. ACA also suppressed phospho-p65 NF-κB activation, suggesting a potential mechanism for its action. PMID:22704648

  17. Alpha-1 Antitrypsin Test

    MedlinePlus

    ... measures the level of the protein AAT in blood. Alpha-1 antitrypsin phenotype testing evaluates the amount and type of AAT being produced and compares it to normal patterns. Alpha-1 antitrypsin genotype testing ( DNA testing) can ...

  18. Alpha-1 antitrypsin test

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/003715.htm Alpha-1 antitrypsin test To use the sharing features on this page, please enable JavaScript. Alpha-1 antitrypsin is a laboratory test to measure the ...

  19. Parallel channels and rate-limiting steps in complex protein folding reactions: prolyl isomerization and the alpha subunit of Trp synthase, a TIM barrel protein.

    PubMed

    Wu, Ying; Matthews, C Robert

    2002-10-18

    A kinetic folding mechanism for the alpha subunit of tryptophan synthase (alphaTS) from Escherichia coli, involving four parallel channels with multiple native, intermediate and unfolded forms, has recently been proposed. The hypothesis that cis/trans isomerization of several Xaa-Pro peptide bonds is the source of the multiple folding channels was tested by measuring the sensitivity of the three rate-limiting phases (tau(1), tau(2), tau(3)) to catalysis by cyclophilin, a peptidyl-prolyl isomerase. Although the absence of catalysis for the tau(1) (fast) phase leaves its assignment ambiguous, our previous mutational analysis demonstrated its connection to the unique cis peptide bond preceding proline 28. The acceleration of the tau(2) (medium) and tau(3) (slow) refolding phases by cyclophilin demonstrated that cis/trans prolyl isomerization is also the source of these phases. A collection of proline mutants, which covered all of the remaining 18 trans proline residues of alphaTS, was constructed to obtain specific assignments for these phases. Almost all of the mutant proteins retained the complex equilibrium and kinetic folding properties of wild-type alphaTS; only the P217A, P217G and P261A mutations caused significant changes in the equilibrium free energy surface. Both the P78A and P96A mutations selectively eliminated the tau(1) folding phase, while the P217M and P261A mutations eliminated the tau(2) and tau(3) folding phases, respectively. The redundant assignment of the tau(1) phase to Pro28, Pro78 and Pro96 may reflect their mutual interactions in non-random structure in the unfolded state. The non-native cis isomers for Pro217 and Pro261 may destabilize an autonomous C-terminal folding unit, thereby giving rise to kinetically distinct unfolded forms. The nature of the preceding amino acid, the solvent exposure, or the participation in specific elements of secondary structure in the native state, in general, are not determinative of the proline residues whose

  20. Search capability for {eta}{yields}{nu}{sub e,{tau}{nu}e,{tau}}decays in cubic-kilometer neutrino detectors

    SciTech Connect

    Fazely, A. R.; Gunasingha, R. M.; Imlay, R. L.; Muhammad, K. D.; Ter-Antonyan, S. V.; Xu, X.

    2010-06-01

    We investigate the discovery potential of cubic-kilometer neutrino observatories such as IceCube to set stringent limits on the forbidden decays {eta}{yields}{nu}{sub e{nu}e} and {eta}{yields}{nu}{sub {tau}{nu}{tau}.} The signatures for these decays are cascade events resulting from the charged-current reactions of {nu}{sub e}, {nu}{sub {tau},} {nu}{sub e}, and {nu}{sub {tau}}on nuclei in such detectors. Background cascade events are mainly due to {nu}{sub e}'s from atmospheric {mu}, K{sup +}, and K{sub S}{sup 0} decays and to a lesser extent from atmospheric {nu}{sub {mu}}neutral-current interactions with nuclei. A direct upper limit for the branching ratio {eta}{yields}{nu}{sub e,{tau}{nu}e,{tau}}of 6.1x10{sup -4} at 90% CL can be achieved.

  1. Improved measurement of absolute branching fraction of D{sub s}{sup +}{yields}{tau}{sup +}{nu}{sub {tau}}

    SciTech Connect

    Onyisi, P. U. E.; Rosner, J. L.; Alexander, J. P.; Cassel, D. G.; Duboscq, J. E.; Ehrlich, R.; Fields, L.; Galik, R. S.; Gibbons, L.; Gray, R.; Gray, S. W.; Hartill, D. L.; Heltsley, B. K.; Hertz, D.; Hunt, J. M.; Kandaswamy, J.; Kreinick, D. L.; Kuznetsov, V. E.; Ledoux, J.; Mahlke-Krueger, H.

    2009-03-01

    We have studied the leptonic decay D{sub s}{sup +}{yields}{tau}{sup +}{nu}{sub {tau}}, via the decay channel {tau}{sup +}{yields}e{sup +}{nu}{sub e}{nu}{sub {tau}}, using a sample of tagged D{sub s}{sup +} decays collected near the D{sub s}*{sup {+-}}D{sub s}{sup {+-}} peak production energy in e{sup +}e{sup -} collisions with the CLEO-c detector. We obtain B(D{sub s}{sup +}{yields}{tau}{sup +}{nu}{sub {tau}})=(5.30{+-}0.47{+-}0.22)% and determine the decay constant f{sub D{sub s}}=(252.5{+-}11.1{+-}5.2) MeV, where the first uncertainties are statistical and the second are systematic.

  2. Characterization and expression profile of two UDP-glucosyltransferases, UGT85K4 and UGT85K5, catalyzing the last step in cyanogenic glucoside biosynthesis in cassava.

    PubMed

    Kannangara, Rubini; Motawia, Mohammed S; Hansen, Natascha K K; Paquette, Suzanne M; Olsen, Carl E; Møller, Birger L; Jørgensen, Kirsten

    2011-10-01

    Manihot esculenta (cassava) contains two cyanogenic glucosides, linamarin and lotaustralin, biosynthesized from l-valine and l-isoleucine, respectively. In this study, cDNAs encoding two uridine diphosphate glycosyltransferase (UGT) paralogs, assigned the names UGT85K4 and UGT85K5, have been isolated from cassava. The paralogs display 96% amino acid identity, and belong to a family containing cyanogenic glucoside-specific UGTs from Sorghum bicolor and Prunus dulcis. Recombinant UGT85K4 and UGT85K5 produced in Escherichia coli were able to glucosylate acetone cyanohydrin and 2-hydroxy-2-methylbutyronitrile, forming linamarin and lotaustralin. UGT85K4 and UGT85K5 show broad in vitro substrate specificity, as documented by their ability to glucosylate other hydroxynitriles, some flavonoids and simple alcohols. Immunolocalization studies indicated that UGT85K4 and UGT85K5 co-occur with CYP79D1/D2 and CYP71E7 paralogs, which catalyze earlier steps in cyanogenic glucoside synthesis in cassava. These enzymes are all found in mesophyll and xylem parenchyma cells in the first unfolded cassava leaf. In situ PCR showed that UGT85K4 and UGT85K5 are co-expressed with CYP79D1 and both CYP71E7 paralogs in the cortex, xylem and phloem parenchyma, and in specific cells in the endodermis of the petiole of the first unfolded leaf. Based on the data obtained, UGT85K4 and UGT85K5 are concluded to be the UGTs catalyzing in planta synthesis of cyanogenic glucosides. The localization of the biosynthetic enzymes suggests that cyanogenic glucosides may play a role in both defense reactions and in fine-tuning nitrogen assimilation in cassava.

  3. Phosphate analysis and dephosphorylation of modified tau associated with paired helical filaments.

    PubMed

    Ksiezak-Reding, H; Liu, W K; Yen, S H

    1992-12-01

    We performed phosphate analysis of tau proteins isolated from normal human brain, tau proteins associated with paired helical filaments (PHF-tau), and Alzheimer tau not associated with PHF. These tau fractions were of high purity. Normal and Alzheimer tau were purified by heat treatment, acid extraction and calmodulin-affinity chromatography with or without HPLC. Fractions containing primarily PHF-tau polypeptides of 60, 64 and 68 kDa and their degraded fragments were purified either on a sucrose density gradient as filaments (PHF) or by heat treatment and acid extraction as amorphous proteins (PHF-tau). PHF and PHF-tau were found to contain 6-8 mol phosphate/mol protein while normal and Alzheimer tau proteins contained 1.9 and 2.6 mol phosphate/mol protein, respectively. Upon 2-h incubation with alkaline phosphatase, PHF lost two of the phosphate groups without apparent changes in the stability and morphology of PHF. The released phosphate originated from the N-terminal half of PHF-tau as determined by immunoblotting with antibodies to epitopes blocked by phosphorylation. Tau-1 and E-2, and by a prominent shift in the electrophoretic mobility of some fragments of PHF-tau. The shift in mobility was not observed with the C-terminal fragments of 25-26 kDa, which retained the epitope to Tau 46. The results suggest that the phosphorylation sites not affected by phosphatase may be located in the 25-26 kDa C-terminal region of PHF-tau and may play a role in structural stability of PHF.

  4. Tau and muon lepton flavor violations in the littlest Higgs model with T parity

    SciTech Connect

    Goto, Toru; Okada, Yasuhiro; Yamamoto, Yasuhiro

    2011-03-01

    Lepton flavor violation in {tau} and {mu} processes is studied in the littlest Higgs model with T parity. We consider various asymmetries defined in polarized {tau} and {mu} decays. Correlations among branching ratios and asymmetries are shown in the following lepton flavor violation processes: {mu}{sup +}{yields}e{sup +}{gamma}, {mu}{sup +}{yields}e{sup +}e{sup +}e{sup -}, {mu}{sup -}A{yields}e{sup -}A (A=Al, Ti, Au, and Pb), {tau}{sup +}{yields}{mu}{sup +}{gamma}, {tau}{sup +}{yields}{mu}{sup +}{mu}{sup +}{mu}{sup -}, {tau}{sup +}{yields}{mu}{sup +}e{sup +}e{sup -}, {tau}{sup +}{yields}{mu}{sup +}P (P={pi}{sup 0}, {eta} and {eta}{sup '}), {tau}{sup +}{yields}{mu}{sup +}V (V={rho}{sup 0}, {omega} and {phi}), {tau}{sup +}{yields}e{sup +}{gamma}, {tau}{sup +}{yields}e{sup +}e{sup +}e{sup -}, {tau}{sup +}{yields}e{sup +}{mu}{sup +}{mu}{sup -}, {tau}{sup +}{yields}e{sup +}P, {tau}{sup +}{yields}e{sup +}V, {tau}{sup +}{yields}{mu}{sup +}{mu}{sup +}e{sup -} and {tau}{sup +}{yields}e{sup +}e{sup +}{mu}{sup -}. It is shown that large parity asymmetries and time-reversal asymmetries are allowed in {mu}{sup +}{yields}e{sup +}e{sup +}e{sup -}. For {tau} lepton flavor violation processes, sizable asymmetries are possible reflecting characteristic chirality structure of lepton flavor violating interactions in this model.

  5. Propagation of tau pathology in Alzheimer's disease: identification of novel therapeutic targets.

    PubMed

    Pooler, Amy M; Polydoro, Manuela; Wegmann, Susanne; Nicholls, Samantha B; Spires-Jones, Tara L; Hyman, Bradley T

    2013-01-01

    Accumulation and aggregation of the microtubule-associated protein tau are a pathological hallmark of neurodegenerative disorders such as Alzheimer's disease (AD). In AD, tau becomes abnormally phosphorylated and forms inclusions throughout the brain, starting in the entorhinal cortex and progressively affecting additional brain regions as the disease progresses. Formation of these inclusions is thought to lead to synapse loss and cell death. Tau is also found in the cerebrospinal fluid (CSF), and elevated levels are a biomarker for AD. Until recently, it was thought that the presence of tau in the CSF was due to the passive release of aggregated tau from dead or dying tangle-bearing neurons. However, accumulating evidence from different AD model systems suggests that tau is actively secreted and transferred between synaptically connected neurons. Transgenic mouse lines with localized expression of aggregating human tau in the entorhinal cortex have demonstrated that, as these animals age, tau becomes mislocalized from axons to cell bodies and dendrites and that human tau-positive aggregates form first in the entorhinal cortex and later in downstream projection targets. Numerous in vitro and in vivo studies have provided insight into the mechanisms by which tau may be released and internalized by neurons and have started to provide insight into how tau pathology may spread in AD. In this review, we discuss the evidence for regulated tau release and its specific uptake by neurons. Furthermore, we identify possible therapeutic targets for preventing the propagation of tau pathology, as inhibition of tau transfer may restrict development of tau tangles in a small subset of neurons affected in early stages of AD and therefore prevent widespread neuron loss and cognitive dysfunction associated with later stages of the disease.

  6. Orbit-averaged drift kinetic equation for the study of alpha-particle transport in tokamaks

    SciTech Connect

    Sager, G.T.; Miley, G.H. . Fusion Studies Lab.); Burrell, K.H. )

    1990-11-01

    Neoclassical transport of minority suprathermal alpha particles is investigated. This paper departs from previous investigations in that (a) the banana-width ordering parameter {rho}{sub {theta}}/L is not formally restricted to be a small parameter and (b) a linearized collision operator that retains the effects of pitch-angle scattering, electron and ion drag, and speed diffusion is used. A step model approximation for the large-aspect-ratio, circular-cross-section tokamak magnetic field is adopted to simplify the orbit-averaging procedure. Assuming that the suprathermal alphas are in the banana regime, an asymptotic expansion in {tau}{sub B}/{tau}{sub S} {much lt} l is carried out.

  7. VizieR Online Data Catalog: CaII and Hα data for dK5/dM4 stars (Houdebine, 2012)

    NASA Astrophysics Data System (ADS)

    Houdebine, E. R.

    2013-03-01

    We use 665 high-resolution spectra for 60 different dM4 stars and 1088 high-resolution spectra for 97 different dK5 stars from the European Southern Observatory (ESO) and Observatoire de Haute Provence (OHP) data bases. We present 179 new measurements of the CaII resonance lines and 615 new measurements of the Hα line for dM4 stars. We also present 701 new measurements of the CaII resonance lines and 1088 new measurements of the Hα line for dK5 stars. We also compiled other measurements available in the literature. (6 data files).

  8. First-in-man tau vaccine targeting structural determinants essential for pathological tau–tau interaction reduces tau oligomerisation and neurofibrillary degeneration in an Alzheimer’s disease model

    PubMed Central

    2014-01-01

    Introduction We have identified structural determinants on tau protein that are essential for pathological tau–tau interaction in Alzheimer’s disease (AD). These regulatory domains, revealed by monoclonal antibody DC8E8, represent a novel target for tau-directed therapy. In order to validate this target, we have developed an active vaccine, AADvac1. Methods A tau peptide encompassing the epitope revealed by DC8E8 was selected for the development of an active vaccine targeting structural determinants on mis-disordered tau protein that are essential for pathological tau–tau interaction. The efficacy of the vaccine was tested in a transgenic rat model of human tauopathies. Toxicology and safety pharmacology studies were conducted under good laboratory practice conditions in multiple rodent and nonrodent species. Results We have administered the tau peptide vaccine to a rat model of AD to investigate whether the vaccine can improve its clinical, histopathological and biochemical AD phenotype. Our results show that vaccination induced a robust protective humoral immune response, with antibodies discriminating between pathological and physiological tau. Active immunotherapy reduced the levels of tau oligomers and the extent of neurofibrillary pathology in the brains of transgenic rats. Strikingly, immunotherapy has reduced AD-type hyperphosphorylation of tau by approximately 95%. Also, the tau peptide vaccine improved the clinical phenotype of transgenic animals. Toxicology and safety pharmacology studies showed an excellent safety and tolerability profile of the AADvac1 vaccine. Conclusions Active immunisation targeting crucial domains of Alzheimer tau eliminated tau aggregation and neurofibrillary pathology. Most importantly, the AD type of tau hyperphosphorylation was abolished by vaccination across a wide range of AD phospho-epitopes. Our results demonstrate that active immunisation led to elimination of all major hallmarks of neurofibrillary pathology, which

  9. The Alpha Centauri System.

    ERIC Educational Resources Information Center

    Soderblom, David R.

    1987-01-01

    Describes the Alpha Centauri star system, which is the closest star system to the sun. Discusses the difficulties associated with measurements involving Alpha Centauri, along with some of the recent advances in stellar seismology. Raises questions about the possibilities of planets around Alpha Centauri. (TW)

  10. Chronic Repetitive Mild Traumatic Brain Injury Results in Reduced Cerebral Blood Flow, Axonal Injury, Gliosis, and Increased T-Tau and Tau Oligomers.

    PubMed

    Ojo, Joseph O; Mouzon, Benoit; Algamal, Moustafa; Leary, Paige; Lynch, Cillian; Abdullah, Laila; Evans, James; Mullan, Michael; Bachmeier, Corbin; Stewart, William; Crawford, Fiona

    2016-07-01

    Exposure to repetitive mild traumatic brain injury (mTBI) is a risk factor for chronic traumatic encephalopathy, which is characterized by patchy deposition of hyperphosphorylated tau aggregates in neurons and astrocytes at the depths of cortical sulci. We developed an mTBI paradigm to explore effects of repetitive concussive-type injury over several months in mice with a human tau genetic background (hTau). Two injuries were induced in the hTau mice weekly over a period of 3 or 4 months and the effects were compared with those in noninjured sham animals. Behavioral and in vivo measures and detailed neuropathological assessments were conducted 6 months after the first injury. Our data confirm impairment in cerebral blood flow and white matter damage. This was accompanied by a 2-fold increase in total tau levels and mild increases in tau oligomers/conformers and pTau (Thr231) species in brain gray matter. There was no evidence of neurofibrillary/astroglial tangles, neuropil threads, or perivascular foci of tau immunoreactivity. There were neurobehavioral deficits (ie, disinhibition and impaired cognitive performance) in the mTBI animals. These data support the relevance of this new mTBI injury model for studying the consequences of chronic repetitive mTBI in humans, and the role of tau in TBI. PMID:27251042

  11. Chronic Repetitive Mild Traumatic Brain Injury Results in Reduced Cerebral Blood Flow, Axonal Injury, Gliosis, and Increased T-Tau and Tau Oligomers.

    PubMed

    Ojo, Joseph O; Mouzon, Benoit; Algamal, Moustafa; Leary, Paige; Lynch, Cillian; Abdullah, Laila; Evans, James; Mullan, Michael; Bachmeier, Corbin; Stewart, William; Crawford, Fiona

    2016-07-01

    Exposure to repetitive mild traumatic brain injury (mTBI) is a risk factor for chronic traumatic encephalopathy, which is characterized by patchy deposition of hyperphosphorylated tau aggregates in neurons and astrocytes at the depths of cortical sulci. We developed an mTBI paradigm to explore effects of repetitive concussive-type injury over several months in mice with a human tau genetic background (hTau). Two injuries were induced in the hTau mice weekly over a period of 3 or 4 months and the effects were compared with those in noninjured sham animals. Behavioral and in vivo measures and detailed neuropathological assessments were conducted 6 months after the first injury. Our data confirm impairment in cerebral blood flow and white matter damage. This was accompanied by a 2-fold increase in total tau levels and mild increases in tau oligomers/conformers and pTau (Thr231) species in brain gray matter. There was no evidence of neurofibrillary/astroglial tangles, neuropil threads, or perivascular foci of tau immunoreactivity. There were neurobehavioral deficits (ie, disinhibition and impaired cognitive performance) in the mTBI animals. These data support the relevance of this new mTBI injury model for studying the consequences of chronic repetitive mTBI in humans, and the role of tau in TBI.

  12. Identification of small molecule inhibitors of Tau aggregation by targeting monomeric Tau as a potential therapeutic approach for Tauopathies

    PubMed Central

    Pickhardt, Marcus; Neumann, Thomas; Schwizer, Daniel; Callaway, Kari; Vendruscolo, Michele; Schenk, Dale; George-Hyslop, Peter; Mandelkow, Eva M.; Dobson, Christopher M.; McConlogue, Lisa; Mandelkow, Eckhard; Tóth, Gergely

    2016-01-01

    A potential strategy to alleviate the aggregation of intrinsically disordered proteins (IDPs) is to maintain the native functional state of the protein by small molecule binding. However, the targeting of the native state of IDPs by small molecules has been challenging due to their heterogeneous conformational ensembles. To tackle this challenge, we applied a high-throughput chemical microarray surface plasmon resonance imaging screen to detect the binding between small molecules and monomeric full-length Tau, a protein linked with the onset of a range of Tauopathies. The screen identified a novel set of drug-like fragment and lead-like compounds that bound to Tau. We verified that the majority of these hit compounds reduced the aggregation of different Tau constructs in vitro and in N2a cells. These results demonstrate that Tau is a viable receptor of drug-like small molecules. The drug discovery approach that we present can be applied to other IDPs linked to other misfolding diseases such as Alzheimer’s and Parkinson’s diseases. PMID:26510979

  13. Identification of Small Molecule Inhibitors of Tau Aggregation by Targeting Monomeric Tau As a Potential Therapeutic Approach for Tauopathies

    PubMed Central

    Pickhardt, Marcus; Neumann, Thomas; Schwizer, Daniel; Callaway, Kari; Vendruscolo, Michele; Schenk, Dale; St. George-Hyslop, Peter; Mandelkow, Eva M.; Dobson, Christopher M.; McConlogue, Lisa; Mandelkow, Eckhard; Tóth, Gergely

    2015-01-01

    A potential strategy to alleviate the aggregation of intrinsically disordered proteins (IDPs) is to maintain the native functional state of the protein by small molecule binding. However, the targeting of the native state of IDPs by small molecules has been challenging due to their heterogeneous conformational ensembles. To tackle this challenge, we applied a high-throughput chemical microarray surface plasmon resonance imaging screen to detect the binding between small molecules and monomeric full-length Tau, a protein linked with the onset of a range of Tauopathies. The screen identified a novel set of drug-like fragment and lead-like compounds that bound to Tau. We verified that the majority of these hit compounds reduced the aggregation of different Tau constructs in vitro and in N2a cells. These results demonstrate that Tau is a viable receptor of drug-like small molecules. The drug discovery approach that we present can be applied to other IDPs linked to other misfolding diseases such as Alzheimer’s and Parkinson’s diseases.

  14. Identification of Novel Tau Interactions with Endoplasmic Reticulum Proteins in Alzheimer’s Disease Brain

    PubMed Central

    Meier, Shelby; Bell, Michelle; Lyons, Danielle N.; Ingram, Alexandria; Chen, Jing; Gensel, John C.; Zhu, Haining; Nelson, Peter T.; Abisambra, Jose F.

    2016-01-01

    Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that is pathologically characterized by the formation of extracellular amyloid plaques and intraneuronal tau tangles. We recently identified that tau associates with proteins known to participate in endoplasmic reticulum (ER)-associated degradation (ERAD); consequently, ERAD becomes dysfunctional and causes neurotoxicity. We hypothesized that tau associates with other ER proteins, and that this association could also lead to cellular dysfunction in AD. Portions of human AD and non-demented age matched control brains were fractionated to obtain microsomes, from which tau was co-immunoprecipitated. Samples from both conditions containing tau and its associated proteins were analyzed by mass spectrometry. In total, we identified 91 ER proteins that co-immunoprecipitated with tau; 15.4% were common between AD and control brains, and 42.9% only in the AD samples. The remainder, 41.8% of the proteins, was only seen in the control brain samples. We identified a variety of previously unreported interactions between tau and ER proteins. These proteins participate in over sixteen functional categories, the most abundant being involved in RNA translation. We then determined that association of tau with these ER proteins was different between the AD and control samples. We found that tau associated equally with the ribosomal protein L28 but more robustly with the ribosomal protein P0. These data suggest that the differential association between tau and ER proteins in disease could reveal the pathogenic processes by which tau induces cellular dysfunction. PMID:26402096

  15. Kaon content of three-prong decays of the tau lepton

    SciTech Connect

    Eastman, J.J.

    1990-12-01

    We present a series of measurements involving the production of charged kaons in three-prong hadronic decays of the {tau} lepton. The data sample was obtained with the TPC/Two-Gamma detector facility at PEP. We set a limit on the branching fraction BR({tau}{sup {minus}} {yields} {nu}{sub {tau}}K{sup {minus}}K{sup 0}) < 0.26% at the 95% confidence level. The process {tau}{sup {minus}} {yields} {nu}{sub {tau}}K{sup {minus}}K{sup 0} is related via SU(3) to the second-class current decay {tau}{sup {minus}} {yields} {nu}{sub {tau}}{pi}{sup {minus}}{eta}. We also present new measurements of the three-prong branching fractions BR({tau}{sup {minus}} {yields} {nu}{sub {tau}}K{sup {minus}}{pi}{sup +}{pi}{sup {minus}} + neutrals) = 0.70 (+0.20/{minus}0.17)% and BR({tau}{sup {minus}} {yields} {nu}{sub {tau}}K{sup {minus}}K{sup +}{pi}{sup {minus}} + neutrals) = 0.16 (+0.10/{minus}0.07)%. 68 refs., 29 figs., 15 tabs.

  16. Disruption of neuronal function by soluble hyperphosphorylated tau in a Drosophila model of tauopathy.

    PubMed

    Cowan, Catherine M; Chee, Francis; Shepherd, David; Mudher, Amritpal

    2010-04-01

    Axonal microtubules are essential for transport of materials to the synapse. Compromised microtubules and synaptic loss have been demonstrated in AD (Alzheimer's disease), which is believed to contribute to cognitive dysfunction before neuronal death in the early stages of the disease. The mechanism by which hyperphosphorylated tau, the building block of neurofibrillary tangles, one of the pathological hallmarks of AD, disrupts neuronal and synaptic function is unclear. There is a theory that hyperphosphorylated tau does not bind effectively to microtubules and is no longer able to function in stabilizing them, thus axonal transport can no longer proceed efficiently. This leads to synaptic dysfunction. We have tested this theory in a Drosophila model of tauopathies in which we expressed human tau (h-tau). Using this model, we have tested all aspects of this hypothesis and have demonstrated that axonal transport does become compromised in the presence of hyperphosphorylated h-tau and this leads to synaptic and behavioural defects. We are currently investigating the mechanism by which hyperphosphorylated h-tau mediates this effect and are preliminary data indicate that this entails phospho-tau-mediated effects that are predicted by the tau-microtubule hypothesis, as well as novel effects. These deleterious effects of h-tau occur in the absence of tau filaments and before neuronal death. This sequence of pathogenic events may constitute the mechanism by which abnormal tau disrupts neuronal and synaptic function and contributes to cognitive impairment before neuronal death in the early stages of tauopathies such as AD. PMID:20298222

  17. Alternative conformations of the Tau repeat domain in complex with an engineered binding protein.

    PubMed

    Grüning, Clara S R; Mirecka, Ewa A; Klein, Antonia N; Mandelkow, Eckhard; Willbold, Dieter; Marino, Stephen F; Stoldt, Matthias; Hoyer, Wolfgang

    2014-08-15

    The aggregation of Tau into paired helical filaments is involved in the pathogenesis of several neurodegenerative diseases, including Alzheimer disease. The aggregation reaction is characterized by conformational conversion of the repeat domain, which partially adopts a cross-β-structure in the resulting amyloid-like fibrils. Here, we report the selection and characterization of an engineered binding protein, β-wrapin TP4, targeting the Tau repeat domain. TP4 was obtained by phage display using the four-repeat Tau construct K18ΔK280 as a target. TP4 binds K18ΔK280 as well as the longest isoform of human Tau, hTau40, with nanomolar affinity. NMR spectroscopy identified two alternative TP4-binding sites in the four-repeat domain, with each including two hexapeptide motifs with high β-sheet propensity. Both binding sites contain the aggregation-determining PHF6 hexapeptide within repeat 3. In addition, one binding site includes the PHF6* hexapeptide within repeat 2, whereas the other includes the corresponding hexapeptide Tau(337-342) within repeat 4, denoted PHF6**. Comparison of TP4-binding with Tau aggregation reveals that the same regions of Tau are involved in both processes. TP4 inhibits Tau aggregation at substoichiometric concentration, demonstrating that it interferes with aggregation nucleation. This study provides residue-level insight into the interaction of Tau with an aggregation inhibitor and highlights the structural flexibility of Tau.

  18. Appoptosin-Mediated Caspase Cleavage of Tau Contributes to Progressive Supranuclear Palsy Pathogenesis

    PubMed Central

    Zhao, Yingjun; Tseng, I-Chu; Heyser, Charles J.; Rockenstein, Edward; Mante, Michael; Adame, Anthony; Zheng, Qiuyang; Huang, Timothy; Wang, Xin; Arslan, Pharhad E.; Chakrabarty, Paramita; Wu, Chengbiao; Bu, Guojun; Mobley, William C.; Zhang, Yun-wu; George-Hyslop, Peter St.; Masliah, Eliezer; Fraser, Paul; Xu, Huaxi

    2015-01-01

    SUMMARY Progressive supranuclear palsy (PSP) is a movement disorder characterized by tau neuropathology where the underlying mechanism is unknown. A single nucleotide polymorphism (rs1768208 C/T) has been identified as a strong risk factor for PSP. Here, we identified a much higher T-allele occurrence and increased levels of the pro-apoptotic protein appoptosin in PSP patients. Elevations in appoptosin correlate with activated caspase-3 and caspase-cleaved tau levels. Appoptosin overexpression increased caspase-mediated tau cleavage, tau aggregation and synaptic dysfunction, whereas appoptosin deficiency reduced tau cleavage and aggregation. Appoptosin transduction impaired multiple motor functions and exacerbated neuropathology in tau-transgenic mice in a manner dependent on caspase-3 and tau. Increased appoptosin and caspase-3 cleaved tau were also observed in brain samples of patients with Alzheimer’s disease and frontotemporal dementia with tau inclusions. Our findings reveal a novel role for appoptosin in neurological disorders with tau neuropathology, linking caspase-3-mediated tau cleavage to synaptic dysfunction and behavioral/motor defects. PMID:26335643

  19. Effect size of memory deficits in mice with adult-onset P301L tau expression.

    PubMed

    Hunsberger, Holly C; Rudy, Carolyn C; Weitzner, Daniel S; Zhang, Chong; Tosto, David E; Knowlan, Kevin; Xu, Ying; Reed, Miranda N

    2014-10-01

    Transgenic mice expressing mutations in tau have yielded essential discoveries for Alzheimer's disease. One of the most commonly used tau mouse models is the tet-off Tg(tauP301L)4510 model that expresses P301L human tau driven by the calcium-calmodulin kinase IIα (CaMKIIα) promoter system. Tau expression in this model is regulatable, allowing for suppression of mutant tau expression until adulthood and prevention of possible developmental alterations resulting from P301L tau expression during development. Here, we compared the effect and sample sizes needed for three learning and memory tasks in mice with adult-onset P301L tau expression. Our findings indicate that the Incremental Repeated Acquisition (IRA) and trace fear conditioning tasks, neither of which have previously been published with these mice, were highly sensitive to P301L tau expression, whereas the Morris water maze, the most commonly used task with this model, was the least sensitive. Memory deficits were observed at a time when tau pathology was subtle and prior to readily detectable neuronal loss. Thus, we provide essential information (effect and sample sizes needed) for establishing experimental designs at a time point when memory deficits are likely to go undetected if inadequate sample sizes are used. Our work also suggests the tet-off Tg4510 model provides a way to avoid mutant tau expression during the perinatal and early postnatal stages, thereby preventing possible developmental alterations unrelated to Alzheimer's disease.

  20. Calpain-Mediated Tau Cleavage: A Mechanism Leading to Neurodegeneration Shared by Multiple Tauopathies

    PubMed Central

    Ferreira, Adriana; Bigio, Eileen H

    2011-01-01

    Tau dysfunction has been associated with a host of neurodegenerative diseases called tauopathies. These diseases share, as a common pathological hallmark, the presence of intracellular aggregates of hyperphosphorylated tau in affected brain areas. Aside from tau hyperphosphorylation, little is known about the role of other posttranslational modifications in tauopathies. Recently, we obtained data suggesting that calpain-mediated tau cleavage leading to the generation of a neurotoxic tau fragment might play an important role in Alzheimer’s disease. In the current study, we assessed the presence of this tau fragment in several tauopathies. Our results show high levels of the 17-kDa tau fragment and enhanced calpain activity in the temporal cortex of AD patients and in brain samples obtained from patients with other tauopathies. In addition, our data suggest that this fragment could partially inhibit tau aggregation. Conversely, tau aggregation might prevent calpain-mediated cleavage, establishing a feedback circuit that might lead to the accumulation of this toxic tau fragment. Collectively, these data suggest that the mechanism underlying the generation of the 17-kDa neurotoxic tau fragment might be part of a conserved pathologic process shared by multiple tauopathies. PMID:21442128

  1. Altered phosphorylation of. tau. protein in heat-shocked rats and patients with Alzheimer disease

    SciTech Connect

    Papasozomenos, S.C.; Yuan Su Baylor College of Medicine, Houston, TX )

    1991-05-15

    Six hours after heat shocking 2- to 3-month-old male and female Sprague-Dawley rats at 42C for 15 min, the authors analyzed {tau} protein immunoreactivity in SDS extracts of cerebrums and peripheral nerves by using immunoblot analysis and immunohistochemistry with the anti-{tau} monoclonal antibody Tau-1, which recognizes a phosphate-dependent nonphosphorylated epitope, and with {sup 125}I-labeled protein A. In the cerebal extracts, the authors found altered phosphorylation of {tau} in heat-shocked females, characterized by a marked reduction in the amount of nonphosphorylated {tau}, a doubling of the ratio of total (phosphorylated plus nonphosphorylated) {tau} to nonphosphorylated {tau}, and the appearance of the slowest moving phosphorylated {tau} polypeptide (68 kDa). Similar, but milder, changes were observed in male rats. Quantitative immunoblot analysis of cortex and the underlying white matter with Tau-1 and {sup 125}I-labeled protein A showed that the amount of phosphorylated {tau} progressively increased in the Alzheimer disease-affected cerebral cortex, while concurrently a proportionally lesser amount of {tau} entered the white matter axons. The similar findings for the rat heat-shock model and Alzheimer disease suggest that life stressors may play a role in the etiopathogenesis of Alzheimer's disease.

  2. Appoptosin-Mediated Caspase Cleavage of Tau Contributes to Progressive Supranuclear Palsy Pathogenesis.

    PubMed

    Zhao, Yingjun; Tseng, I-Chu; Heyser, Charles J; Rockenstein, Edward; Mante, Michael; Adame, Anthony; Zheng, Qiuyang; Huang, Timothy; Wang, Xin; Arslan, Pharhad E; Chakrabarty, Paramita; Wu, Chengbiao; Bu, Guojun; Mobley, William C; Zhang, Yun-Wu; St George-Hyslop, Peter; Masliah, Eliezer; Fraser, Paul; Xu, Huaxi

    2015-09-01

    Progressive supranuclear palsy (PSP) is a movement disorder characterized by tau neuropathology where the underlying mechanism is unknown. An SNP (rs1768208 C/T) has been identified as a strong risk factor for PSP. Here, we identified a much higher T-allele occurrence and increased levels of the pro-apoptotic protein appoptosin in PSP patients. Elevations in appoptosin correlate with activated caspase-3 and caspase-cleaved tau levels. Appoptosin overexpression increased caspase-mediated tau cleavage, tau aggregation, and synaptic dysfunction, whereas appoptosin deficiency reduced tau cleavage and aggregation. Appoptosin transduction impaired multiple motor functions and exacerbated neuropathology in tau-transgenic mice in a manner dependent on caspase-3 and tau. Increased appoptosin and caspase-3-cleaved tau were also observed in brain samples of patients with Alzheimer's disease and frontotemporal dementia with tau inclusions. Our findings reveal a novel role for appoptosin in neurological disorders with tau neuropathology, linking caspase-3-mediated tau cleavage to synaptic dysfunction and behavioral/motor defects. PMID:26335643

  3. Identification and isolation of a hyperphosphorylated, conformationally changed intermediate of human protein tau expressed in yeast.

    PubMed

    Vandebroek, Tom; Vanhelmont, Thomas; Terwel, Dick; Borghgraef, Peter; Lemaire, Katleen; Snauwaert, Johan; Wera, Stefaan; Van Leuven, Fred; Winderickx, Joris

    2005-08-30

    Hyperphosphorylation and aggregation of protein tau are typical for neurodegenerative tauopathies, including Alzheimer's disease (AD). We demonstrate here that human tau expressed in yeast acquired pathological phosphoepitopes, assumed a pathological conformation, and formed aggregates. These processes were modulated by yeast kinases Mds1 and Pho85, orthologues of GSK-3beta and cdk5, respectively. Surprisingly, inactivation of Pho85 increased phosphorylation of tau-4R, concomitant with increased conformational change defined by antibody MC1 and a 40-fold increase in aggregation. Soluble protein tau, purified from yeast lacking PHO85, spontaneously and rapidly formed tau filaments in vitro. Further fractionation of tau by anion-exchange chromatography yielded a hyperphosphorylated monomeric subfraction, termed hP-tau/MC1, with slow electrophoretic mobility and enriched with all major epitopes, including MC1. Isolated hP-tau/MC1 vastly accelerated in vitro aggregation of wild-type tau-4R, demonstrating its functional capacity to initiate aggregation, as well as its structural stability. Combined, this novel yeast model recapitulates hyperphosphorylation, conformation, and aggregation of protein tau, provides insight in molecular changes crucial in tauopathies, offers a source for isolation of modified protein tau, and has potential for identification of modulating compounds and genes.

  4. Phosphorylation of Tau at Thr212, Thr231, and Ser262 Combined Causes Neurodegeneration*

    PubMed Central

    Alonso, Alejandra D.; Di Clerico, John; Li, Bin; Corbo, Christopher P.; Alaniz, Maria E.; Grundke-Iqbal, Inge; Iqbal, Khalid

    2010-01-01

    Abnormal hyperphosphorylation of the microtubule-associated protein Tau is a hallmark of Alzheimer disease and related diseases called tauopathies. As yet, the exact mechanism by which this pathology causes neurodegeneration is not understood. The present study provides direct evidence that Tau abnormal hyperphosphorylation causes its aggregation, breakdown of the microtubule network, and cell death and identifies phosphorylation sites involved in neurotoxicity. We generated pseudophosphorylated Tau proteins by mutating Ser/Thr to Glu and, as controls, to Ala. These mutations involved one, two, or three pathological phosphorylation sites by site-directed mutagenesis using as backbones the wild type or FTDP-17 mutant R406W Tau. Pseudophosphorylated and corresponding control Tau proteins were expressed transiently in PC12 and CHO cells. We found that a single phosphorylation site alone had little influence on the biological activity of Tau, except Thr212, which, upon mutation to Glu in the R406W background, induced Tau aggregation in cells, suggesting phosphorylation at this site along with a modification on the C-terminal of the protein facilitates self-assembly of Tau. The expression of R406W Tau pseudophosphorylated at Thr212, Thr231, and Ser262 triggered caspase-3 activation in as much as 85% of the transfected cells, whereas the corresponding value for wild type pseudophosphorylated Tau was 30%. Cells transfected with pseudophosphorylated Tau became TUNEL-positive. PMID:20663882

  5. Direct Evidence of Internalization of Tau by Microglia In Vitro and In Vivo.

    PubMed

    Bolós, Marta; Llorens-Martín, María; Jurado-Arjona, Jerónimo; Hernández, Félix; Rábano, Alberto; Avila, Jesús

    2015-01-01

    The microtubule-associated protein (MAP) tau plays a critical role in the pathogenesis of tauopathies. Excess tau can be released into the extracellular medium in a physiological or pathological manner to be internalized by surrounding neurons-a process that contributes to the spread of this protein throughout the brain. Such spreading may correlate with the progression of the abovementioned diseases. In addition to neurons, tau can be internalized into other cells. Here we demonstrate that microglia take up tau in vitro and in vivo. In this regard, microglia from primary cultures internalized soluble (human recombinant tau42) and insoluble (homogenates derived from human AD brain) tau in vitro. Furthermore, using stereotaxic injection of tau in mice in vivo, we show that murine microglia internalize human tau. In addition, we demonstrate, for the first time, that microglia colocalize with various forms of tau in postmortem brain tissue of patients with Alzheimer's disease and non-demented control subjects. Our data reveal a potential role of microglia in the internalization of tau that might be relevant for the design of strategies to enhance the clearance of extracellular tau in neurodegenerative diseases characterized by the accumulation of this protein.

  6. Toxic tau oligomer formation blocked by capping of cysteine residues with 1,2-dihydroxybenzene groups

    PubMed Central

    Soeda, Yoshiyuki; Yoshikawa, Misato; Almeida, Osborne F. X.; Sumioka, Akio; Maeda, Sumihiro; Osada, Hiroyuki; Kondoh, Yasumitsu; Saito, Akiko; Miyasaka, Tomohiro; Kimura, Tetsuya; Suzuki, Masaaki; Koyama, Hiroko; Yoshiike, Yuji; Sugimoto, Hachiro; Ihara, Yasuo; Takashima, Akihiko

    2015-01-01

    Neurofibrillary tangles, composed of hyperphosphorylated tau fibrils, are a pathological hallmark of Alzheimer's disease; the neurofibrillary tangle load correlates strongly with clinical progression of the disease. A growing body of evidence indicates that tau oligomer formation precedes the appearance of neurofibrillary tangles and contributes to neuronal loss. Here we show that tau oligomer formation can be inhibited by compounds whose chemical backbone includes 1,2-dihydroxybenzene. Specifically, we demonstrate that 1,2-dihydroxybenzene-containing compounds bind to and cap cysteine residues of tau and prevent its aggregation by hindering interactions between tau molecules. Further, we show that orally administered DL-isoproterenol, an adrenergic receptor agonist whose skeleton includes 1,2-dihydroxybenzene and which penetrates the brain, reduces the levels of detergent-insoluble tau, neuronal loss and reverses neurofibrillary tangle-associated brain dysfunction. Thus, compounds that target the cysteine residues of tau may prove useful in halting the progression of Alzheimer's disease and other tauopathies. PMID:26671725

  7. Reconstruction of {tau}-tilde{sub 1} mass at the LHC

    SciTech Connect

    Djilkibaev, R. M.; Konoplich, R. V.

    2011-01-15

    The cascade mass reconstruction approach was used for mass reconstruction of the lightest {tau}-tilde produced at the LHC in the cascade decay g-tilde {yields} b-tildeb {yields} {chi}-tilde{sub 2}{sup 0}bb {yields} {tau}-tilde{sub 1}{tau}bb {yields} {chi}-tilde{sub 1}{sup 0}{tau}{tau}bb. The {tau}-tilde{sub 1} mass was reconstructed assuming that masses of gluino, bottom squark, and two lightest neutralinos were reconstructed in advance. SUSY data sample sets for the SU(3) model point containing 160k events each were generated which corresponded to an integrated luminosity of about 8 fb{sup -1} at 14 TeV. These events were passed through the AcerDET detector simulator, which parametrized the response of a generic LHC detector. The mass of the {tau}-tilde{sub 1} was reconstructed with a precision of about 20% on average.

  8. Lepton flavor violating Higgs bosons and {tau}{yields}{mu}{gamma}

    SciTech Connect

    Davidson, Sacha; Grenier, Gerald

    2010-05-01

    We update phenomenological constraints on a two Higgs doublet model with lepton flavor nonconserving Yukawa couplings. We review that tan{beta} is ambiguous in such 'type III' models, and define it from the {tau} Yukawa coupling. The neutral scalars {phi} could be searched for at hadron colliders in {phi}{yields}{tau}{mu} and are constrained by the rare decay {tau}{yields}{mu}{gamma}. The Feynman diagrams for the collider process, with Higgs production via gluon fusion, are similar to the two-loop ''Barr-Zee'' diagrams, which contribute to {tau}{yields}{mu}{gamma}. Some ''tuning'' is required to obtain a collider cross section of order the standard model expectation for {sigma}(gg{yields}h{sub SM{yields}{tau}}{sup +{tau}-}), while agreeing with the current bound from {tau}{yields}{mu}{gamma}.

  9. Tau-based therapeutics for Alzheimer's disease: active and passive immunotherapy.

    PubMed

    Panza, Francesco; Solfrizzi, Vincenzo; Seripa, Davide; Imbimbo, Bruno P; Lozupone, Madia; Santamato, Andrea; Tortelli, Rosanna; Galizia, Ilaria; Prete, Camilla; Daniele, Antonio; Pilotto, Alberto; Greco, Antonio; Logroscino, Giancarlo

    2016-09-01

    Pharmacological manipulation of tau protein in Alzheimer's disease included microtubule-stabilizing agents, tau protein kinase inhibitors, tau aggregation inhibitors, active and passive immunotherapies and, more recently, inhibitors of tau acetylation. Animal studies have shown that both active and passive approaches can remove tau pathology and, in some cases, improve cognitive function. Two active vaccines targeting either nonphosphorylated (AAD-vac1) and phosphorylated tau (ACI-35) have entered Phase I testing. Notwithstanding, the recent discontinuation of the monoclonal antibody RG7345 for Alzheimer's disease, two other antitau antibodies, BMS-986168 and C2N-8E12, are also currently in Phase I testing for progressive supranuclear palsy. After the recent impressive results in animal studies obtained by salsalate, the dimer of salicylic acid, inhibitors of tau acetylation are being actively pursued. PMID:27485083

  10. Evidence of a massive planet candidate orbiting the young active K5V star BD+20 1790

    NASA Astrophysics Data System (ADS)

    Hernán-Obispo, M.; Gálvez-Ortiz, M. C.; Anglada-Escudé, G.; Kane, S. R.; Barnes, J. R.; de Castro, E.; Cornide, M.

    2010-03-01

    Context. BD+20 1790 is a young active, metal-rich, late-type K5Ve star. We have undertaken a study of stellar activity and kinematics for this star over the past few years. Previous results show a high level of stellar activity, with the presence of prominence-like structures, spots on the surface, and strong flare events, despite the moderate rotational velocity of the star. In addition, radial velocity variations with a semi-amplitude of up to 1 km s-1 were detected. Aims: We investigate the nature of these radial velocity variations, in order to determine whether they are due to stellar activity or the reflex motion of the star induced by a companion. Methods: We have analysed high-resolution echelle spectra by measuring stellar activity indicators and computing radial velocity (RV) and bisector velocity spans. Two-band photometry was also obtained to produce the light curve and determine the photometric period. Results: Based upon the analysis of the bisector velocity span, as well as spectroscopic indices of chromospheric indicators, Ca ii H & K, Hα, and taking the photometric analysis into account, we report that the best explanation for the RV variation is the presence of a substellar companion. The Keplerian fit of the RV data yields a solution for a close-in massive planet with an orbital period of 7.78 days. The presence of the close-in massive planet could also be an interpretation for the high level of stellar activity detected. Since the RV data are not part of a planet search programme, we can consider our results as a serendipitous evidence of a planetary companion. To date, this is the youngest main sequence star for which a planetary candidate has been reported. Based on observations collected at the German-Spanish Astronomical Center, Calar Alto, jointly operated by the Max-Planck-Institut für Astronomie Heidelberg and the Instituto de Astrofísica de Andalucía (CSIC). Based on observations made with the Italian Telescopio Nazionale Galileo

  11. Expression of A152T human tau causes age-dependent neuronal dysfunction and loss in transgenic mice.

    PubMed

    Maeda, Sumihiro; Djukic, Biljana; Taneja, Praveen; Yu, Gui-Qiu; Lo, Iris; Davis, Allyson; Craft, Ryan; Guo, Weikun; Wang, Xin; Kim, Daniel; Ponnusamy, Ravikumar; Gill, T Michael; Masliah, Eliezer; Mucke, Lennart

    2016-04-01

    A152T-variant human tau (hTau-A152T) increases risk for tauopathies, including Alzheimer's disease. Comparing mice with regulatable expression of hTau-A152T or wild-type hTau (hTau-WT), we find age-dependent neuronal loss, cognitive impairments, and spontaneous nonconvulsive epileptiform activity primarily in hTau-A152T mice. However, overexpression of either hTau species enhances neuronal responses to electrical stimulation of synaptic inputs and to an epileptogenic chemical. hTau-A152T mice have higher hTau protein/mRNA ratios in brain, suggesting that A152T increases production or decreases clearance of hTau protein. Despite their functional abnormalities, aging hTau-A152T mice show no evidence for accumulation of insoluble tau aggregates, suggesting that their dysfunctions are caused by soluble tau. In human amyloid precursor protein (hAPP) transgenic mice, co-expression of hTau-A152T enhances risk of early death and epileptic activity, suggesting copathogenic interactions between hTau-A152T and amyloid-β peptides or other hAPP metabolites. Thus, the A152T substitution may augment risk for neurodegenerative diseases by increasing hTau protein levels, promoting network hyperexcitability, and synergizing with the adverse effects of other pathogenic factors. PMID:26931567

  12. Dual-specificity tyrosine phosphorylation-regulated kinase 1A (Dyrk1A) enhances tau expression.

    PubMed

    Qian, Wei; Jin, Nana; Shi, Jianhua; Yin, Xiaomin; Jin, Xiaoxia; Wang, Shibao; Cao, Maohong; Iqbal, Khalid; Gong, Cheng-Xin; Liu, Fei

    2013-01-01

    Microtubule-associated protein tau is found to be accumulated and aggregated in the brains of individuals with Alzheimer's disease and related tauopathies. Dual-specificity tyrosine-phosphorylation regulated kinase 1A (Dyrk1A) is overexpressed in Down syndrome and may play a critical role in the early onset of tau pathology in this disease. To investigate the effect of Dyrk1A on tau expression, we co-expressed different isoforms of tau with Dyrk1A in HEK-293FT cells and measured the mRNA and protein levels of tau using RT-PCR and Western blots, respectively. We further investigated the mechanism of regulation of tau expression by Dyrk1A. We found that Dyrk1A enhanced tau expression in a dose-dependent manner. The enhancement did not require the kinase activity of Dyrk1A. Dyrk1A increased the expression of tau isoforms containing exon 10 to a larger extent than isoforms lacking exon 10. The expression of endogenous tau in neuronal cells was also regulated by Dyrk1A, and increased tau levels were found in the brains of Ts65Dn mice that overexpress Dyrk1A due to partial trisomy of chromosome 16. Dyrk1A did not enhance tau gene transcription, but increased tau mRNA stability. These results suggest that Dyrk1A enhances tau expression by stabilizing its mRNA and provides a novel insight into the regulation of tau expression and a molecular mechanism of tauopathies. PMID:23948904

  13. Wake County Public School System K-5 Assessment Results: 2009-10. Measuring Up. E&R Report No. 10.19

    ERIC Educational Resources Information Center

    Rhea, Anisa

    2010-01-01

    Moderate to high percentages of Wake County Public School (WCPSS) students demonstrated grade-level performance on K-5 assessments in 2009-10. Results indicate very slight changes from prior years. The percentage of students proficient in reading book level and mathematics strands increased very slightly since 2007-08. Modest declines in…

  14. Kaposi's sarcoma-associated herpesvirus K3 and K5 proteins down regulate both DC-SIGN and DC-SIGNR.

    PubMed

    Lang, Sabine M; Bynoe, Meisha O F; Karki, Roshan; Tartell, Michael A; Means, Robert E

    2013-01-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of multicentric Castleman's disease, primary effusion lymphoma and Kaposi's sarcoma. In this study, we show that like the C-type lectin DC-SIGN, the closely related DC-SIGNR can also enhance KSHV infection. Following infection, they are both targeted for down modulation and our data indicate that the KSHV MARCH-family ubiquitin ligase K5 is mediating this regulation and subsequent targeting for degradation of DC-SIGN and DC-SIGNR in the context of the virus. The closely related viral K3 protein, is also able to target these lectins in exogenous expressions studies, but only weakly during viral infection. In addition to requiring a functional RING-CH domain, several protein trafficking motifs in the C-terminal region of both K3 and K5 are important in regulation of DC-SIGN and DC-SIGNR. Further exploration of this modulation revealed that DC-SIGN is endocytosed from the cell surface in THP-1 monocytes, but degraded from an internal location with minimal endocytosis in HEK-293 cells. Pull-down data indicate that both K3 and K5 preferentially associate with immature forms of the lectins, mediating their ubiquitylation and degradation. Together, these data emphasize the molecular complexities of K3 and K5, while expanding the repertoire of targets of these two viral proteins. PMID:23460925

  15. Clonal differentiation of uropathogenic Escherichia coli isolates of serotype O6:K5 by fimbrial antigen typing and DNA long-range mapping techniques.

    PubMed

    Zingler, G; Blum, G; Falkenhagen, U; Orskov, I; Orskov, F; Hacker, J; Ott, M

    1993-03-01

    Escherichia coli isolates of serotype O6:K5 are the most common causative agents of cystitis and pyelonephritis in adults. To answer the question, as to whether strains of this particular serotype represent one special clonal group, out of a collection of 34 serotype O6:K5 isolates [Zingler et al. (1990) Zentralbl. Bakteriol Mikrobiol Hyg [A] 274:372-381] 15 strains were selected and analyzed in detail. The flagellar (H) antigen and the outer membrane protein (OMP) pattern were determined. Further serum resistance properties and the genetic presence and expression of other virulence factors, including hemolysin, aerobactin, P fimbriae, S/F1C fimbriae and type 1 fimbriae was evaluated. In addition the XbaI-macrorestriction pattern of ten representative isolates was elaborated and the fimbrial (F) antigen type of the P fimbriae was determined, to obtain the complete O:K:H:F pattern. These analyses could clearly show that the O6:K5 isolates do not represent one clonal group. The XbaI-macrorestriction profiles were heterogeneous and marked differences in the hybridization patterns, using virulence-associated gene probes in Southern hybridization of long-range-separated genomic DNA, were observed among the strains. However, some of strains showed similarities in the genomic profiles, arguing for clonal groupings among the O6:K5 isolates. Interestingly the strains grouped together exhibited the same fimbrial F type that many indicate a coincidence of this phenotypic trait with clonality.

  16. Expanding the Role of K-5 Science Instruction in Educational Reform: Implications of an Interdisciplinary Model for Integrating Science and Reading

    ERIC Educational Resources Information Center

    Romance, Nancy R.; Vitale, Michael R.

    2012-01-01

    Addressed is the current practice in educational reform of reducing time for science instruction in favor of traditional reading/language arts instruction. In contrast, presented is an evidence-based rationale for increasing instructional time for K-5 science instruction as an educational reform initiative. Overviewed are consensus…

  17. Laying the Foundation for Successful Non-Academic Writing: Professional Communication Principles in the K-5 Curricula of the McKinney Independent School District

    ERIC Educational Resources Information Center

    Trevino, Marlea

    2009-01-01

    Traditionally, K-5 students' writing has had a primarily academic aim--to help students master concepts and express themselves. Even if students take a professional writing course later, they typically do not have the opportunity to practice--over the long period of time mastery requires--the non-academic writing skills they will be required to…

  18. The relationship between cerebrospinal fluid markers of Alzheimer pathology and positron emission tomography tau imaging.

    PubMed

    Gordon, Brian A; Friedrichsen, Karl; Brier, Matthew; Blazey, Tyler; Su, Yi; Christensen, Jon; Aldea, Patricia; McConathy, Jonathan; Holtzman, David M; Cairns, Nigel J; Morris, John C; Fagan, Anne M; Ances, Beau M; Benzinger, Tammie L S

    2016-08-01

    The two primary molecular pathologies in Alzheimer's disease are amyloid-β plaques and tau-immunoreactive neurofibrillary tangles. Investigations into these pathologies have been restricted to cerebrospinal fluid assays, and positron emission tomography tracers that can image amyloid-β plaques. Tau tracers have recently been introduced into the field, although the utility of the tracer and its relationship to other Alzheimer biomarkers are still unknown. Here we examined tau deposition in 41 cognitively normal and 11 cognitively impaired older adults using the radioactive tau ligand (18)F-AV-1451 (previously known as T807) who also underwent a lumbar puncture to assess cerebrospinal fluid levels of total tau (t-tau), phosphorylated tau181 (p-tau181) and amyloid-β42 Voxel-wise statistical analyses examined spatial patterns of tau deposition associated with cognitive impairment. We then related the amount of tau tracer uptake to levels of cerebrospinal fluid biomarkers. All analyses controlled for age and gender and, when appropriate, the time between imaging and lumbar puncture assessments. Symptomatic individuals (Clinical Dementia Rating > 0) demonstrated markedly increased levels of tau tracer uptake. This elevation was most prominent in the temporal lobe and temporoparietal junction, but extended more broadly into parietal and frontal cortices. In the entire cohort, there were significant relationships among all cerebrospinal fluid biomarkers and tracer uptake, notably for tau-related cerebrospinal fluid markers. After controlling for levels of amyloid-β42, the correlations with tau uptake were r = 0.490 (P < 0.001) for t-tau and r = 0.492 (P < 0.001) for p-tau181 Within the cognitively normal cohort, levels of amyloid-β42, but not t-tau or p-tau181, were associated with elevated tracer binding that was confined primarily to the medial temporal lobe and adjacent neocortical regions. AV-1451 tau binding in the medial temporal, parietal, and frontal cortices

  19. Tau Pathology is Present In Vivo and Develops In Vitro in Sensory Neurons from Human P301S Tau Transgenic Mice: A System for Screening Drugs against Tauopathies

    PubMed Central

    Mellone, Manuela; Kestoras, Dimitra; Andrews, Melissa R.; Dassie, Elisa; Crowther, R. Anthony; Stokin, Gorazd B.; Tinsley, Jon; Horne, Graeme; Goedert, Michel

    2013-01-01

    Intracellular tau aggregates are the neuropathological hallmark of several neurodegenerative diseases, including Alzheimer's disease, progressive supranuclear palsy, and cases of frontotemporal dementia, but the link between these aggregates and neurodegeneration remains unclear. Neuronal models recapitulating the main features of tau pathology are necessary to investigate the molecular mechanisms of tau malfunction, but current models show little and inconsistent spontaneous tau aggregation. We show that dorsal root ganglion (DRG) neurons in transgenic mice expressing human P301S tau (P301S-htau) develop tau pathology similar to that found in brain and spinal cord and a significant reduction in mechanosensation occurs before detectable fibrillar tau formation. DRG neuronal cultures established from adult P301S-htau mice at different ages retained the pattern of aberrant tau found in vivo. Moreover, htau became progressively hyperphosphorylated over 2 months in vitro beginning with nonsymptomatic neurons, while hyperphosphorylated P301S-htau-positive neurons from 5-month-old mice cultured for 2 months died preferentially. P301S-htau-positive neurons grew aberrant axons, including spheroids, typically found in human tauopathies. Neurons cultured at advanced stages of tau pathology showed a 60% decrease in the fraction of moving mitochondria. SEG28019, a novel O-GlcNAcase inhibitor, reduced steady-state pSer396/pSer404 phosphorylation over 7 weeks in a significant proportion of DRG neurons showing for the first time the possible beneficial effect of prolonged dosing of O-GlcNAcase inhibitor in vitro. Our system is unique in that fibrillar tau forms without external manipulation and provides an important new tool for understanding the mechanisms of tau dysfunction and for screening of compounds for treatment of tauopathies. PMID:24227726

  20. Disruption of Escherichia coli Nissle 1917 K5 capsule biosynthesis, through loss of distinct kfi genes, modulates interaction with intestinal epithelial cells and impact on cell health.

    PubMed

    Nzakizwanayo, Jonathan; Kumar, Sandeep; Ogilvie, Lesley A; Patel, Bhavik A; Dedi, Cinzia; Macfarlane, Wendy M; Jones, Brian V

    2015-01-01

    Escherichia coli Nissle 1917 (EcN) is among the best characterised probiotics, with a proven clinical impact in a range of conditions. Despite this, the mechanisms underlying these "probiotic effects" are not clearly defined. Here we applied random transposon mutagenesis to identify genes relevant to the interaction of EcN with intestinal epithelial cells. This demonstrated mutants disrupted in the kfiB gene, of the K5 capsule biosynthesis cluster, to be significantly enhanced in attachment to Caco-2 cells. However, this phenotype was distinct from that previously reported for EcN K5 deficient mutants (kfiC null mutants), prompting us to explore further the role of kfiB in EcN:Caco-2 interaction. Isogenic mutants with deletions in kfiB (EcNΔkfiB), or the more extensively characterised K5 capsule biosynthesis gene kfiC (EcNΔkfiC), were both shown to be capsule deficient, but displayed divergent phenotypes with regard to impact on Caco-2 cells. Compared with EcNΔkfiC and the EcN wild-type, EcNΔkfiB exhibited significantly greater attachment to Caco-2 cells, as well as apoptotic and cytotoxic effects. In contrast, EcNΔkfiC was comparable to the wild-type in these assays, but was shown to induce significantly greater COX-2 expression in Caco-2 cells. Distinct differences were also apparent in the pervading cell morphology and cellular aggregation between mutants. Overall, these observations reinforce the importance of the EcN K5 capsule in host-EcN interactions, but demonstrate that loss of distinct genes in the K5 pathway can modulate the impact of EcN on epithelial cell health. PMID:25790373

  1. Disruption of Escherichia coli Nissle 1917 K5 capsule biosynthesis, through loss of distinct kfi genes, modulates interaction with intestinal epithelial cells and impact on cell health.

    PubMed

    Nzakizwanayo, Jonathan; Kumar, Sandeep; Ogilvie, Lesley A; Patel, Bhavik A; Dedi, Cinzia; Macfarlane, Wendy M; Jones, Brian V

    2015-01-01

    Escherichia coli Nissle 1917 (EcN) is among the best characterised probiotics, with a proven clinical impact in a range of conditions. Despite this, the mechanisms underlying these "probiotic effects" are not clearly defined. Here we applied random transposon mutagenesis to identify genes relevant to the interaction of EcN with intestinal epithelial cells. This demonstrated mutants disrupted in the kfiB gene, of the K5 capsule biosynthesis cluster, to be significantly enhanced in attachment to Caco-2 cells. However, this phenotype was distinct from that previously reported for EcN K5 deficient mutants (kfiC null mutants), prompting us to explore further the role of kfiB in EcN:Caco-2 interaction. Isogenic mutants with deletions in kfiB (EcNΔkfiB), or the more extensively characterised K5 capsule biosynthesis gene kfiC (EcNΔkfiC), were both shown to be capsule deficient, but displayed divergent phenotypes with regard to impact on Caco-2 cells. Compared with EcNΔkfiC and the EcN wild-type, EcNΔkfiB exhibited significantly greater attachment to Caco-2 cells, as well as apoptotic and cytotoxic effects. In contrast, EcNΔkfiC was comparable to the wild-type in these assays, but was shown to induce significantly greater COX-2 expression in Caco-2 cells. Distinct differences were also apparent in the pervading cell morphology and cellular aggregation between mutants. Overall, these observations reinforce the importance of the EcN K5 capsule in host-EcN interactions, but demonstrate that loss of distinct genes in the K5 pathway can modulate the impact of EcN on epithelial cell health.

  2. Heteromeric complexes of alpha 5 and/or alpha 7 subunits. Effects of calcium and potential role in nicotine-induced presynaptic facilitation.

    PubMed

    Girod, R; Crabtree, G; Ernstrom, G; Ramirez-Latorre, J; McGehee, D; Turner, J; Role, L

    1999-04-30

    Nicotine alters a broad spectrum of behaviors, including attention, arousal, anxiety, and memory. The cellular physiology of nicotine is comparably diverse: nicotine interacts with an array of ionotropic receptors whose gating can lead to direct depolarization of neurons or to an indirect modulation of neuronal excitability by presynaptic facilitation. Furthermore, as many laboratories have shown, the alpha- and beta-type subunits that comprise neuronal nicotinic acetylcholine receptors (nAChRs) are encoded by multiple, homologous genes, yielding at least seven alpha and three beta subunits, distinct in primary sequence. nAChRs that differ in subunit composition differ in pharmacology, conductance, and kinetics as well as in their permeability to and modulation by calcium. We will first discuss recent studies on the biophysics of a special (peculiar?) subset of nAChRs, focusing on heteromeric nAChRs comprised of alpha 4 beta 2 +/- alpha 5 or alpha 7 +/- beta 2 and alpha 5. These nAChR channel subtypes are potently and differentially modulated by changes in intracellular calcium ([Ca]). Thus, the Po, tau o, and desensitization kinetics of alpha 4 beta 2 channels are altered by changes in [Ca]int from 0 to 50 microM; nAChRs that include the alpha 5 subunit are oppositely regulated. Mutagenesis of specific residues within the M1 and M2 domain of alpha 4, beta 2, and alpha 5 suggest a possible Ca binding "pocket." The assembly of functional nAChRs that include alpha 5 and/or alpha 7 and the potential role of these novel heteromeric complexes in presynaptic facilitation will also be presented.

  3. Characterization of Novel CSF Tau and ptau Biomarkers for Alzheimer’s Disease

    PubMed Central

    Guss, Valerie; Lanzetti, Anthony J.; Berisha, Flora; Neely, Robert J.; Slemmon, J. Randall; Portelius, Erik; Zetterberg, Henrik; Blennow, Kaj; Soares, Holly; Ahlijanian, Michael; Albright, Charles F.

    2013-01-01

    Cerebral spinal fluid (CSF) Aβ42, tau and p181tau are widely accepted biomarkers of Alzheimer’s disease (AD). Numerous studies show that CSF tau and p181tau levels are elevated in mild-to-moderate AD compared to age-matched controls. In addition, these increases might predict preclinical AD in cognitively normal elderly. Despite their importance as biomarkers, the molecular nature of CSF tau and ptau is not known. In the current study, reverse-phase high performance liquid chromatography was used to enrich and concentrate tau prior to western-blot analysis. Multiple N-terminal and mid-domain fragments of tau were detected in pooled CSF with apparent sizes ranging from <20 kDa to ~40 kDa. The pattern of tau fragments in AD and control samples were similar. In contrast, full-length tau and C-terminal-containing fragments were not detected. To quantify levels, five tau ELISAs and three ptau ELISAs were developed to detect different overlapping regions of the protein. The discriminatory potential of each assay was determined using 20 AD and 20 age-matched control CSF samples. Of the tau ELISAs, the two assays specific for tau containing N-terminal sequences, amino acids 9-198 (numbering based on tau 441) and 9-163, exhibited the most significant differences between AD and control samples. In contrast, CSF tau was not detected with an ELISA specific for a more C-terminal region (amino acids 159-335). Significant discrimination was also observed with ptau assays measuring amino acids 159-p181 and 159-p231. Interestingly, the discriminatory potential of p181 was reduced when measured in the context of tau species containing amino acids 9-p181. Taken together, these results demonstrate that tau in CSF occurs as a series of fragments and that discrimination of AD from control is dependent on the subset of tau species measured. These assays provide novel tools to investigate CSF tau and ptau as biomarkers for other neurodegenerative diseases. PMID:24116116

  4. Epitope mapping and structural basis for the recognition of phosphorylated tau by the anti‐tau antibody AT8

    PubMed Central

    Teplyakov, Alexey; Ernst, Robin; Wu, Sheng‐Jiun; Lacy, Eilyn R.; Liu, Xuesong; Vandermeeren, Marc; Mercken, Marc; Luo, Jinquan; Sweet, Raymond W.; Gilliland, Gary L.

    2016-01-01

    ABSTRACT Microtubule‐associated protein tau becomes abnormally phosphorylated in Alzheimer's disease and other tauopathies and forms aggregates of paired helical filaments (PHF‐tau). AT8 is a PHF‐tau‐specific monoclonal antibody that is a commonly used marker of neuropathology because of its recognition of abnormally phosphorylated tau. Previous reports described the AT8 epitope to include pS202/pT205. Our studies support and extend previous findings by also identifying pS208 as part of the binding epitope. We characterized the phosphoepitope of AT8 through both peptide binding studies and costructures with phosphopeptides. From the cocrystal structure of AT8 Fab with the diphosphorylated (pS202/pT205) peptide, it appeared that an additional phosphorylation at S208 would also be accommodated by AT8. Phosphopeptide binding studies showed that AT8 bound to the triply phosphorylated tau peptide (pS202/pT205/pS208) 30‐fold stronger than to the pS202/pT205 peptide, supporting the role of pS208 in AT8 recognition. We also show that the binding kinetics of the triply phosphorylated peptide pS202/pT205/pS208 was remarkably similar to that of PHF‐tau. The costructure of AT8 Fab with a pS202/pT205/pS208 peptide shows that the interaction interface involves all six CDRs and tau residues 202–209. All three phosphorylation sites are recognized by AT8, with pT205 acting as the anchor. Crystallization of the Fab/peptide complex under acidic conditions shows that CDR‐L2 is prone to unfolding and precludes peptide binding, and may suggest a general instability in the antibody. Proteins 2016; 84:427–434. © 2016 The Authors. Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc. PMID:26800003

  5. Dietary cholesterol and its effect on tau protein: a study in apolipoprotein E-deficient and P301L human tau mice.

    PubMed

    Glöckner, Frauke; Meske, Volker; Lütjohann, Dieter; Ohm, Thomas G

    2011-04-01

    Apolipoprotein E (ApoE) is the major cholesterol transporter in the brain. There is epidemiological and experimental evidence for involvement of cholesterol metabolism in the development and progression of Alzheimer disease. A dietary effect on tau phosphorylation or aggregation, or a role of apoE in tau metabolism, has been studied experimentally, but the data are ambiguous. To elucidate the relationship between cholesterol and tau, we studied mice expressing P301L mutant human tau but not apoE (htau-ApoE) and P301L mice with wild-type ApoE (htau- ApoE); both genotypes develop neuron cytoskeletal changes similar to those found in Alzheimer disease. Mice were kept on a cholesterol-enriched diet or control diet for 15 weeks. The numbers of neurons with hyperphosphorylated and conformationally changed tau in the cerebral cortex were assessed by immunohistochemistry, and sterol levels were determined. Highly elevated dietary serum cholesterol levels enhanced ongoing tau pathology in htau-ApoE mice; this effect correlated with elevated brain cholesterol metabolite 27-hydroxycholesterol levels. Apolipoprotein E deficiency promoted significant increases of tau phosphorylation and conformational changes in mice on a control diet. In htau-ApoE mice on the high cholesterol regimen, brain oxysterol levels were less than in htau-ApoE mice, and the numbers of neurons with pathologically altered tau were similar to those in htau-ApoE mice on the high-cholesterol diet.

  6. Antibody-Med