SHiP: a new facility with a dedicated detector for studying tau-neutrino properties and nucleon structure functions

NASA Astrophysics Data System (ADS)

Bick, Daniel; SHiP Collaboration

2017-09-01

SHiP is a new general purpose fixed target facility, whose Technical Proposal has been recently reviewed by the CERN SPS Committee, who recommended that the experiment proceeds further to a Comprehensive Design phase. In its initial phase, the 400 GeV proton beam extracted from the SPS will be dumped on a heavy target with the aim of integrating 2 × 1020 pot in 5 years. A dedicated detector downstream of the target will allow to probe a variety of models with light long-lived exotic particles and masses below a few GeV/c2. Another dedicated detector will allow the study of neutrino cross-sections and angular distributions, which was the focus of the poster. ντ deep inelastic scattering cross sections will be measured with a statistics 1000 times larger than currently available, with the extraction of the F 4 and F 5 structure functions, never measured so far and allow for new tests of lepton non-universality with sensitivity to BSM physics. Moreover, ντ ’s will be distinguished from {\\displaystyle \\bar{ν }}τ ’s, thus providing the first observation of the {\\displaystyle \\bar{ν }}τ . With νµ scattering it will be possible to reduce by about 50% the current uncertainty on the strange content of the nucleon in the range of the x variable between 0.05 and 0.3, complementary to LHC measurements. The detector will be based on several techniques developed for the OPERA experiment at LNGS.

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

PubMed Central

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

2015-01-01

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

Effects of antibodies to phosphorylated and non-phosphorylated tau on in vitro tau phosphorylation at Serine-199: Preliminary report.

PubMed

Loeffler, David A; Smith, Lynnae M; Klaver, Andrea C; Martić, Sanela

2015-07-01

Phosphorylation of multiple amino acids on tau protein ("hyperphosphorylation") is required for the development of tau pathology in Alzheimer's disease. Administration of anti-tau antibodies to transgenic "tauopathy mice" has been shown to reduce their tau pathology but the mechanisms responsible are unclear. To examine the effects of anti-tau antibodies on tau phosphorylation, we used western blots to study the effects of three antibodies to phosphorylated tau (pTau), namely anti-pTau S199, T231, and S396, and three antibodies to non-phosphorylated tau on in vitro phosphorylation of recombinant human tau-441 at S199. Inclusion of an anti-pTau T231 antibody in the phosphorylation reaction reduced the intensity of monomeric pTau S199 in western blots of denaturing gels, but the other antibodies had no apparent effects on this process. Surprisingly, including all three anti-phospho-tau antibodies in the reaction did not reduce the intensity of the monomer band, possibly due to steric hindrance between the antibodies. These preliminary findings suggest that anti-tau antibodies may have minimal direct effects on tau phosphorylation. Limitations of using western blots to examine the effects of anti-tau antibodies on this process were found to include between-experiment variability in pTau band densities and poor resolution of high molecular weight pTau oligomers. The presence of bands representing immunoglobulins as well as pTau may also complicate interpretation of the western blots. Further studies are indicated to examine the effects of anti-pTau antibodies on phosphorylation of other tau amino acids in addition to S199. Copyright © 2015 Elsevier Inc. All rights reserved.

Sources of extracellular tau and its signaling.

PubMed

Avila, Jesús; Simón, Diana; Díaz-Hernández, Miguel; Pintor, Jesús; Hernández, Félix

2014-01-01

The pathology associated with tau protein, tauopathy, has been recently analyzed in different disorders, leading to the suggestion that intracellular and extracellular tau may itself be the principal agent in the transmission and spreading of tauopathies. Tau pathology is based on an increase in the amount of tau, an increase in phosphorylated tau, and/or an increase in aggregated tau. Indeed, phosphorylated tau protein is the main component of tau aggregates, such as the neurofibrillary tangles present in the brain of Alzheimer's disease patients. It has been suggested that intracellular tau could be toxic to neurons in its phosphorylated and/or aggregated form. However, extracellular tau could also damage neurons and since neuronal death is widespread in Alzheimer's disease, mainly among cholinergic neurons, these cells may represent a possible source of extracellular tau. However, other sources of extracellular tau have been proposed that are independent of cell death. In addition, several ways have been proposed for cells to interact with, transmit, and spread extracellular tau, and to transduce signals mediated by this tau. In this work, we will discuss the role of extracellular tau in the spreading of the tau pathology.

CONSTRAINING THE EMISSIVITY OF ULTRAHIGH ENERGY COSMIC RAYS IN THE DISTANT UNIVERSE WITH THE DIFFUSE GAMMA-RAY EMISSION

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang Xiangyu; Liu Ruoyu; Aharonian, Felix

Ultrahigh cosmic rays (UHECRs) with energies {approx}> 10{sup 19} eV emitted at cosmological distances will be attenuated by cosmic microwave and infrared background radiation through photohadronic processes. Lower energy extragalactic cosmic rays ({approx}10{sup 18}-10{sup 19} eV) can only travel a linear distance smaller than {approx}Gpc in a Hubble time due to the diffusion if the extragalactic magnetic fields are as strong as nano-Gauss. These prevent us from directly observing most of the UHECRs in the universe, and thus the observed UHECR intensity reflects only the emissivity in the nearby universe within hundreds of Mpc. However, UHECRs in the distant universe,more » through interactions with the cosmic background photons, produce UHE electrons and gamma rays that in turn initiate electromagnetic cascades on cosmic background photons. This secondary cascade radiation forms part of the extragalactic diffuse GeV-TeV gamma-ray radiation and, unlike the original UHECRs, is observable. Motivated by new measurements of extragalactic diffuse gamma-ray background radiation by Fermi/Large Area Telescope, we obtained upper limit placed on the UHECR emissivity in the distant universe by requiring that the cascade radiation they produce not exceed the observed levels. By comparison with the gamma-ray emissivity of candidate UHECR sources (such as gamma-ray bursts (GRBs) and active galactic nuclei) at high redshifts, we find that the obtained upper limit for a flat proton spectrum is {approx_equal} 10{sup 1.5} times larger than the gamma-ray emissivity in GRBs and {approx_equal} 10 times smaller than the gamma-ray emissivity in BL Lac objects. In the case of iron nuclei composition, the derived upper limit of UHECR emissivity is a factor of 3-5 times higher. Robust upper limit on the cosmogenic neutrino flux is further obtained, which is marginally reachable by the Icecube detector and the next-generation detector JEM-EUSO.« less

C3I (Command, Control, Communications and Intelligence) Teradata Study.

DTIC Science & Technology

1986-03-01

data storage capacity of one trillion bytes. The largest configuration currently built consists of 60 processors and 60 disks. .--. ,[ -... "I i The DBC... FMEA ) was developed to l indicate potential points of failure in the configuration and their - effects on total system operation. -"ince the contract did...number or IrPs and AMPs Int is the Integer function Thus, for a maximum configuration (see Section 3.3) of 1024 processors, there are ten tiers in Uhe

Comparing Plasma Phospho Tau, Total Tau, and Phospho Tau-Total Tau Ratio as Acute and Chronic Traumatic Brain Injury Biomarkers.

PubMed

Rubenstein, Richard; Chang, Binggong; Yue, John K; Chiu, Allen; Winkler, Ethan A; Puccio, Ava M; Diaz-Arrastia, Ramon; Yuh, Esther L; Mukherjee, Pratik; Valadka, Alex B; Gordon, Wayne A; Okonkwo, David O; Davies, Peter; Agarwal, Sanjeev; Lin, Fan; Sarkis, George; Yadikar, Hamad; Yang, Zhihui; Manley, Geoffrey T; Wang, Kevin K W; Cooper, Shelly R; Dams-O'Connor, Kristen; Borrasso, Allison J; Inoue, Tomoo; Maas, Andrew I R; Menon, David K; Schnyer, David M; Vassar, Mary J

2017-09-01

Annually in the United States, at least 3.5 million people seek medical attention for traumatic brain injury (TBI). The development of therapies for TBI is limited by the absence of diagnostic and prognostic biomarkers. Microtubule-associated protein tau is an axonal phosphoprotein. To date, the presence of the hypophosphorylated tau protein (P-tau) in plasma from patients with acute TBI and chronic TBI has not been investigated. To examine the associations between plasma P-tau and total-tau (T-tau) levels and injury presence, severity, type of pathoanatomic lesion (neuroimaging), and patient outcomes in acute and chronic TBI. In the TRACK-TBI Pilot study, plasma was collected at a single time point from 196 patients with acute TBI admitted to 3 level I trauma centers (<24 hours after injury) and 21 patients with TBI admitted to inpatient rehabilitation units (mean [SD], 176.4 [44.5] days after injury). Control samples were purchased from a commercial vendor. The TRACK-TBI Pilot study was conducted from April 1, 2010, to June 30, 2012. Data analysis for the current investigation was performed from August 1, 2015, to March 13, 2017. Plasma samples were assayed for P-tau (using an antibody that specifically recognizes phosphothreonine-231) and T-tau using ultra-high sensitivity laser-based immunoassay multi-arrayed fiberoptics conjugated with rolling circle amplification. In the 217 patients with TBI, 161 (74.2%) were men; mean (SD) age was 42.5 (18.1) years. The P-tau and T-tau levels and P-tau-T-tau ratio in patients with acute TBI were higher than those in healthy controls. Receiver operating characteristic analysis for the 3 tau indices demonstrated accuracy with area under the curve (AUC) of 1.000, 0.916, and 1.000, respectively, for discriminating mild TBI (Glasgow Coma Scale [GCS] score, 13-15, n = 162) from healthy controls. The P-tau level and P-tau-T-tau ratio were higher in individuals with more severe TBI (GCS, ≤12 vs 13-15). The P-tau level and P-tau-T-tau ratio outperformed the T-tau level in distinguishing cranial computed tomography-positive from -negative cases (AUC = 0.921, 0.923, and 0.646, respectively). Acute P-tau levels and P-tau-T-tau ratio weakly distinguished patients with TBI who had good outcomes (Glasgow Outcome Scale-Extended GOS-E, 7-8) (AUC = 0.663 and 0.658, respectively) and identified those with poor outcomes (GOS-E, ≤4 vs >4) (AUC = 0.771 and 0.777, respectively). Plasma samples from patients with chronic TBI also showed elevated P-tau levels and a P-tau-T-tau ratio significantly higher than that of healthy controls, with both P-tau indices strongly discriminating patients with chronic TBI from healthy controls (AUC = 1.000 and 0.963, respectively). Plasma P-tau levels and P-tau-T-tau ratio outperformed T-tau level as diagnostic and prognostic biomarkers for acute TBI. Compared with T-tau levels alone, P-tau levels and P-tau-T-tau ratios show more robust and sustained elevations among patients with chronic TBI.

Review: Tau in biofluids - relation to pathology, imaging and clinical features.

PubMed

Zetterberg, H

2017-04-01

Tau is a microtubule-binding protein that is important for the stability of neuronal axons. It is normally expressed within neurons and is also secreted into the brain interstitial fluid that communicates freely with cerebrospinal fluid (CSF) and, in a more restricted manner, blood via the glymphatic clearance system of the brain. In Alzheimer's disease (AD), neuroaxonal degeneration results in increased release of tau from neurons. Furthermore, tau is truncated and phosphorylated, which leads to aggregation of tau in neurofibrillary tangles of the proximal axoplasm. Neuroaxonal degeneration and tangle formation are reflected by increased concentrations of total tau (T-tau, measured using assays that detect most forms of tau) and phospho-tau (P-tau, measured using assays with antibodies specific to phosphorylated forms of tau). In AD CSF, both T-tau and P-tau concentrations are increased. In stroke and other CNS disorders with neuroaxonal injury but without tangles, T-tau is selectively increased, whereas P-tau concentration often stays normal. In tauopathies (diseases with both neurodegeneration and neurofibrillary tangles) other than AD, CSF T-tau and P-tau concentrations are typically unaltered, which is a puzzling result that warrants further investigation. In the current review, I discuss the association of T-tau and P-tau concentrations in body fluids with neuropathological changes, imaging findings and clinical features in AD and other CNS diseases. © 2017 British Neuropathological Society.

GFP-Mutant Human Tau Transgenic Mice Develop Tauopathy Following CNS Injections of Alzheimer's Brain-Derived Pathological Tau or Synthetic Mutant Human Tau Fibrils.

PubMed

Gibbons, Garrett S; Banks, Rachel A; Kim, Bumjin; Xu, Hong; Changolkar, Lakshmi; Leight, Susan N; Riddle, Dawn M; Li, Chi; Gathagan, Ronald J; Brown, Hannah J; Zhang, Bin; Trojanowski, John Q; Lee, Virginia M-Y

2017-11-22

Neurodegenerative proteinopathies characterized by intracellular aggregates of tau proteins, termed tauopathies, include Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD) with tau pathology (FTLD-tau), and related disorders. Pathological tau proteins derived from human AD brains (AD-tau) act as proteopathic seeds that initiate the templated aggregation of soluble tau upon intracerebral injection into tau transgenic (Tg) and wild-type mice, thereby modeling human tau pathology. In this study, we found that aged Tg mice of both sexes expressing human tau proteins harboring a pathogenic P301L MAPT mutation labeled with green fluorescent protein (T40PL-GFP Tg mouse line) exhibited hyperphosphorylated tau mislocalized to the somatodentritic domain of neurons, but these mice did not develop de novo insoluble tau aggregates, which are characteristic of human AD and related tauopathies. However, intracerebral injections of either T40PL preformed fibrils (PFFs) or AD-tau seeds into T40PL-GFP mice induced abundant intraneuronal pathological inclusions of hyperphosphorylated T40PL-GFP. These injections of pathological tau resulted in the propagation of tau pathology from the injection site to neuroanatomically connected brain regions, and these tau inclusions consisted of both T40PL-GFP and WT endogenous mouse tau. Primary neurons cultured from the brains of neonatal T40PL-GFP mice provided an informative in vitro model for examining the uptake and localization of tau PFFs. These findings demonstrate the seeded aggregation of T40PL-GFP in vivo by synthetic PFFs and human AD-tau and the utility of this system to study the neuropathological spread of tau aggregates. SIGNIFICANCE STATEMENT The stereotypical spread of pathological tau protein aggregates have recently been attributed to the transmission of proteopathic seeds. Despite the extensive use of transgenic mouse models to investigate the propagation of tau pathology in vivo , details of the aggregation process such as the early seeding events leading to new tau pathology have remained elusive. This study validates the use of GFP-labeled tau expressed by neurons in vivo and in vitro as models for investigating mechanisms underlying the seeded transmission of tau pathology as well as tau-focused drug discovery to identify disease-modifying therapies for AD and related tauopathies. Copyright © 2017 the authors 0270-6474/17/3711485-10$15.00/0.

GFP-Mutant Human Tau Transgenic Mice Develop Tauopathy Following CNS Injections of Alzheimer's Brain-Derived Pathological Tau or Synthetic Mutant Human Tau Fibrils

PubMed Central

Banks, Rachel A.; Kim, Bumjin; Xu, Hong; Changolkar, Lakshmi; Leight, Susan N.; Riddle, Dawn M.; Li, Chi; Brown, Hannah J.; Zhang, Bin

2017-01-01

Neurodegenerative proteinopathies characterized by intracellular aggregates of tau proteins, termed tauopathies, include Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD) with tau pathology (FTLD-tau), and related disorders. Pathological tau proteins derived from human AD brains (AD-tau) act as proteopathic seeds that initiate the templated aggregation of soluble tau upon intracerebral injection into tau transgenic (Tg) and wild-type mice, thereby modeling human tau pathology. In this study, we found that aged Tg mice of both sexes expressing human tau proteins harboring a pathogenic P301L MAPT mutation labeled with green fluorescent protein (T40PL-GFP Tg mouse line) exhibited hyperphosphorylated tau mislocalized to the somatodentritic domain of neurons, but these mice did not develop de novo insoluble tau aggregates, which are characteristic of human AD and related tauopathies. However, intracerebral injections of either T40PL preformed fibrils (PFFs) or AD-tau seeds into T40PL-GFP mice induced abundant intraneuronal pathological inclusions of hyperphosphorylated T40PL-GFP. These injections of pathological tau resulted in the propagation of tau pathology from the injection site to neuroanatomically connected brain regions, and these tau inclusions consisted of both T40PL-GFP and WT endogenous mouse tau. Primary neurons cultured from the brains of neonatal T40PL-GFP mice provided an informative in vitro model for examining the uptake and localization of tau PFFs. These findings demonstrate the seeded aggregation of T40PL-GFP in vivo by synthetic PFFs and human AD-tau and the utility of this system to study the neuropathological spread of tau aggregates. SIGNIFICANCE STATEMENT The stereotypical spread of pathological tau protein aggregates have recently been attributed to the transmission of proteopathic seeds. Despite the extensive use of transgenic mouse models to investigate the propagation of tau pathology in vivo, details of the aggregation process such as the early seeding events leading to new tau pathology have remained elusive. This study validates the use of GFP-labeled tau expressed by neurons in vivo and in vitro as models for investigating mechanisms underlying the seeded transmission of tau pathology as well as tau-focused drug discovery to identify disease-modifying therapies for AD and related tauopathies. PMID:28986461

Measurement of the absolute branching fraction of Ds+ --> tau+ nutau decay.

PubMed

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; Park, C S; Thorndike, E H; Yang, F; Artuso, M; Blusk, S; Khalil, S; Li, J; Mountain, R; Nisar, S; Randrianarivony, K; Sultana, N; Skwarnicki, T; Stone, S; Wang, J C; Zhang, L M; Bonvicini, G; Cinabro, D; Dubrovin, M; Lincoln, A; Rademacker, J; Asner, D M; Edwards, K W; Naik, P; Reed, J; Briere, R A; Ferguson, T; Tatishvili, G; Vogel, H; Watkins, M E; Rosner, J L; Alexander, J P; Cassel, D G; Duboscq, J E; Ehrlich, R; Fields, L; Gibbons, L; Gray, R; Gray, S W; Hartill, D L; Heltsley, B K; Hertz, D; Jones, C D; Kandaswamy, J; Kreinick, D L; Kuznetsov, V E; Mahlke-Krüger, H; Mohapatra, D; Onyisi, P U E; Patterson, J R; Peterson, D; Riley, D; Ryd, A; Sadoff, A J; Shi, X; Stroiney, S; Sun, W M; Wilksen, T; Athar, S B; Patel, R; Yelton, J; Rubin, P; Eisenstein, B I; Karliner, I; Mehrabyan, S; Lowrey, N; Selen, M; White, E J; Wiss, J; Mitchell, R E; Shepherd, M R; Besson, D; Pedlar, T K; Cronin-Hennessy, D; Gao, K Y; Hietala, J; Kubota, Y; Klein, T; Lang, B W; Poling, R; Scott, A W; Zweber, P; Dobbs, S; Metreveli, Z; Seth, K K; Tomaradze, A; Libby, J; Powell, A; Wilkinson, G

2008-04-25

Using a sample of tagged D(s)(+) decays collected near the D(s)(*+/-)D(s)(-/+) peak production energy in e(+)e(-) collisions with the CLEO-c detector, we study the leptonic decay D(s)(+)-->tau(+)nu(tau) via the decay channel tau(+)-->e(+)nu(e)nu(tau). We measure B(D(s)(+)-->tau(+)nu(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(s)(+)-->mu(+)nu(mu) and D(s)(+)-->tau(+)nu(tau) (via tau(+)-->pi(+)nu(tau)), we determine f(D(s))=(274+/-10+/-5) MeV.

Expression of Tau Pathology-Related Proteins in Different Brain Regions: A Molecular Basis of Tau Pathogenesis.

PubMed

Hu, Wen; Wu, Feng; Zhang, Yanchong; Gong, Cheng-Xin; Iqbal, Khalid; Liu, Fei

2017-01-01

Microtubule-associated protein tau is hyperphosphorylated and aggregated in affected neurons in Alzheimer disease (AD) brains. The tau pathology starts from the entorhinal cortex (EC), spreads to the hippocampus and frontal and temporal cortices, and finally to all isocortex areas, but the cerebellum is spared from tau lesions. The molecular basis of differential vulnerability of different brain regions to tau pathology is not understood. In the present study, we analyzed brain regional expressions of tau and tau pathology-related proteins. We found that tau was hyperphosphorylated at multiple sites in the frontal cortex (FC), but not in the cerebellum, from AD brain. The level of tau expression in the cerebellum was about 1/4 of that seen in the frontal and temporal cortices in human brain. In the rat brain, the expression level of tau with three microtubule-binding repeats (3R-tau) was comparable in the hippocampus, EC, FC, parietal-temporal cortex (PTC), occipital-temporal cortex (OTC), striatum, thalamus, olfactory bulb (OB) and cerebellum. However, the expression level of 4R-tau was the highest in the EC and the lowest in the cerebellum. Tau phosphatases, kinases, microtubule-related proteins and other tau pathology-related proteins were also expressed in a region-specific manner in the rat brain. These results suggest that higher levels of tau and tau kinases in the EC and low levels of these proteins in the cerebellum may accounts for the vulnerability and resistance of these representative brain regions to the development of tau pathology, respectively. The present study provides the regional expression profiles of tau and tau pathology-related proteins in the brain, which may help understand the brain regional vulnerability to tau pathology in neurodegenerative tauopathies.

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

Plasma phospho-tau181 increases with Alzheimer's disease clinical severity and is associated with tau- and amyloid-positron emission tomography.

PubMed

Mielke, Michelle M; Hagen, Clinton E; Xu, Jing; Chai, Xiyun; Vemuri, Prashanthi; Lowe, Val J; Airey, David C; Knopman, David S; Roberts, Rosebud O; Machulda, Mary M; Jack, Clifford R; Petersen, Ronald C; Dage, Jeffrey L

2018-04-04

We examined and compared plasma phospho-tau181 (pTau181) and total tau: (1) across the Alzheimer's disease (AD) clinical spectrum; (2) in relation to brain amyloid β (Aβ) positron emission tomography (PET), tau PET, and cortical thickness; and (3) as a screening tool for elevated brain Aβ. Participants included 172 cognitively unimpaired, 57 mild cognitively impaired, and 40 AD dementia patients with concurrent Aβ PET (Pittsburgh compound B), tau PET (AV1451), magnetic resonance imaging, plasma total tau, and pTau181. Plasma total tau and pTau181 levels were higher in AD dementia patients than those in cognitively unimpaired. Plasma pTau181 was more strongly associated with both Aβ and tau PET. Plasma pTau181 was a more sensitive and specific predictor of elevated brain Aβ than total tau and was as good as, or better than, the combination of age and apolipoprotein E (APOE). Plasma pTau181 may have utility as a biomarker of AD pathophysiology and as a noninvasive screener for elevated brain Aβ. Copyright © 2018. Published by Elsevier Inc.

Intracellular and extracellular microtubule associated protein tau as a therapeutic target in Alzheimer disease and other tauopathies.

PubMed

Avila, Jesús; Pallas, Noemí; Bolós, Marta; Sayas, C Laura; Hernandez, Felix

2016-06-01

Microtubule associated protein tau, a protein mainly expressed in neurons, plays an important role in several diseases related to dementia, named tauopathies. Alzheimer disease is the most relevant tauopathy. The role of tau protein in dementia is now a topic under discussion, and is the focus of this review. We have covered two major areas: tau pathology and tau as a therapeutic target. Tau pathology is mainly related to a gain of toxic function due to an abnormal accumulation, aberrant modifications (such as hyperphosphorylation and truncation, among others) and self-aggregation of tau into oligomers or larger structures. Also, tau can be found extracellularly in a toxic form. Tau-based therapy is mainly centered on avoiding the gain of these toxic functions of tau. Tau therapies are focused on lowering tau levels, mainly of modified tau species that could be toxic for neurons (phosphorylated, truncated or aggregated tau), in intracellular or extracellular form. Decreasing the levels of those toxic species is a possible therapeutic strategy.

Tau Oligomers as Pathogenic Seeds: Preparation and Propagation In Vitro and In Vivo.

PubMed

Gerson, Julia E; Sengupta, Urmi; Kayed, Rakez

2017-01-01

Tau oligomers have been shown to be the main toxic tau species in a number of neurodegenerative disorders. In order to study tau oligomers both in vitro and in vivo, we have established methods for the reliable preparation, isolation, and detection of tau oligomers. Methods for the seeding of tau oligomers, isolation of tau oligomers from tissue, and detection of tau oligomers using tau oligomer-specific antibodies by biochemical and immunohistochemical methods are detailed below.

Tau Antibody Targeting Pathological Species Blocks Neuronal Uptake and Interneuron Propagation of Tau in Vitro.

PubMed

Nobuhara, Chloe K; DeVos, Sarah L; Commins, Caitlin; Wegmann, Susanne; Moore, Benjamin D; Roe, Allyson D; Costantino, Isabel; Frosch, Matthew P; Pitstick, Rose; Carlson, George A; Hock, Christoph; Nitsch, Roger M; Montrasio, Fabio; Grimm, Jan; Cheung, Anne E; Dunah, Anthone W; Wittmann, Marion; Bussiere, Thierry; Weinreb, Paul H; Hyman, Bradley T; Takeda, Shuko

2017-06-01

The clinical progression of Alzheimer disease (AD) is associated with the accumulation of tau neurofibrillary tangles, which may spread throughout the cortex by interneuronal tau transfer. If so, targeting extracellular tau species may slow the spreading of tau pathology and possibly cognitive decline. To identify suitable target epitopes, we tested the effects of a panel of tau antibodies on neuronal uptake and aggregation in vitro. Immunodepletion was performed on brain extract from tau-transgenic mice and postmortem AD brain and added to a sensitive fluorescence resonance energy transfer-based tau uptake assay to assess blocking efficacy. The antibodies reduced tau uptake in an epitope-dependent manner: N-terminal (Tau13) and middomain (6C5 and HT7) antibodies successfully prevented uptake of tau species, whereas the distal C-terminal-specific antibody (Tau46) had little effect. Phosphorylation-dependent (40E8 and p396) and C-terminal half (4E4) tau antibodies also reduced tau uptake despite removing less total tau by immunodepletion, suggesting specific interactions with species involved in uptake. Among the seven antibodies evaluated, 6C5 most efficiently blocked uptake and subsequent aggregation. More important, 6C5 also blocked neuron-to-neuron spreading of tau in a unique three-chamber microfluidic device. Furthermore, 6C5 slowed down the progression of tau aggregation even after uptake had begun. Our results imply that not all antibodies/epitopes are equally robust in terms of blocking tau uptake of human AD-derived tau species. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Curcumin Inhibits Tau Aggregation and Disintegrates Preformed Tau Filaments in vitro.

PubMed

Rane, Jitendra Subhash; Bhaumik, Prasenjit; Panda, Dulal

2017-01-01

The pathological aggregation of tau is a common feature of most of the neuronal disorders including frontotemporal dementia, Parkinson's disease, and Alzheimer's disease. The inhibition of tau aggregation is considered to be one of the important strategies for treating these neurodegenerative diseases. Curcumin, a natural polyphenolic molecule, has been reported to have neuroprotective ability. In this work, curcumin was found to bind to adult tau and fetal tau with a dissociation constant of 3.3±0.4 and 8±1 μM, respectively. Molecular docking studies indicated a putative binding site of curcumin in the microtubule-binding region of tau. Using several complementary techniques, including dynamic light scattering, thioflavin S fluorescence, 90° light scattering, electron microscopy, and atomic force microscopy, curcumin was found to inhibit the aggregation of tau. The dynamic light scattering analysis and atomic force microscopic images revealed that curcumin inhibits the oligomerization of tau. Curcumin also disintegrated preformed tau oligomers. Using Far-UV circular dichroism, curcumin was found to inhibit the β-sheets formation in tau indicating that curcumin inhibits an initial step of tau aggregation. In addition, curcumin inhibited tau fibril formation. Furthermore, the effect of curcumin on the preformed tau filaments was analyzed by atomic force microscopy, transmission electron microscopy, and 90° light scattering. Curcumin treatment disintegrated preformed tau filaments. The results indicated that curcumin inhibited the oligomerization of tau and could disaggregate tau filaments.

Tau Phosphorylation Pathway Genes and Cerebrospinal Fluid Tau Levels in Alzheimer’s Disease

PubMed Central

Bekris, Lynn M.; Millard, Steve; Lutz, Franziska; Li, Gail; Galasko, Doug R.; Farlow, Martin R.; Quinn, Joseph F.; Kaye, Jeffrey A.; Leverenz, James B.; Tsuang, Debby W.; Yu, Chang-En; Peskind, Elaine R.

2013-01-01

Alzheimer’s disease (AD) is characterized by the presence in the brain of amyloid plaques, consisting predominately of the amyloid β peptide (Aβ), and neurofibrillary tangles, consisting primarily of tau. Hyper-phosphorylated-tau (p-tau) contributes to neuronal damage, and both p-tau and total-tau (t-tau) levels are elevated in AD cerebrospinal fluid (CSF) compared to cognitively normal controls. Our hypothesis was that increased ratios of CSF phosphorylated-tau levels relative to total-tau levels correlate with regulatory region genetic variation of kinase or phosphatase genes biologically associated with the phosphorylation status of tau. Eighteen SNPs located within 5′ and 3′ regions of 5 kinase and 4 phosphatase genes, as well as two SNPs within regulatory regions of the MAPT gene were chosen for this analysis. The study sample consisted of 101 AD patients and 169 cognitively normal controls. Rs7768046 in the FYN kinase gene and rs913275 in the PPP2R4 phosphatase gene were both associated with CSF p-tau and t-tau levels in AD. These SNPs were also differentially associated with either CSF t-tau (rs7768046) or CSF p-tau (rs913275) relative to t-tau levels in AD compared to controls. These results suggest that rs7768046 and rs913275 both influence CSF tau levels in an AD-associated manner. PMID:22927204

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

CNS tau efflux via exosomes is likely increased in Parkinson disease but not in Alzheimer disease

PubMed Central

Shi, Min; Kovac, Andrej; Korff, Ane; Cook, Travis J.; Ginghina, Carmen; Bullock, Kristin M.; Yang, Li; Stewart, Tessandra; Zheng, Danfeng; Aro, Patrick; Atik, Anzari; Kerr, Kathleen F.; Zabetian, Cyrus P.; Peskind, Elaine R.; Hu, Shu-Ching; Quinn, Joseph F.; Galasko, Douglas R.; Montine, Thomas J.; Banks, William A.; Zhang, Jing

2016-01-01

Background Alzheimer disease (AD) and Parkinson disease (PD) involve tau pathology. Tau is detectable in blood, but its clearance from neuronal cells and the brain is poorly understood. Methods Tau efflux from the brain to the blood was evaluated by administering radioactively labeled and unlabeled tau intracerebroventricularly in wild-type and tau knock-out mice, respectively. Central nervous system (CNS)-derived tau in L1CAM-containing exosomes was further characterized extensively in human plasma, including by Single Molecule Array technology with 303 subjects. Results The efflux of Tau, including a fraction via CNS-derived L1CAM exosomes, was observed in mice. In human plasma, tau was explicitly identified within L1CAM exosomes. In contrast to AD patients, L1CAM exosomal tau was significantly higher in PD patients than controls, and correlated with cerebrospinal fluid tau. Conclusions Tau is readily transported from the brain to the blood. The mechanisms of CNS tau efflux are likely different between AD and PD. PMID:27234211

Tau mislocalization to dendritic spines mediates synaptic dysfunction independently of neurodegeneration

PubMed Central

Hoover, Brian R.; Reed, Miranda N.; Su, Jianjun; Penrod, Rachel D.; Kotilinek, Linda A.; Grant, Marianne K.; Pitstick, Rose; Carlson, George A.; Lanier, Lorene M.; Yuan, Li-Lian; Ashe, Karen H.; Liao, Dezhi

2010-01-01

The microtubule-associated protein tau accumulates in Alzheimer’s and other fatal dementias, which manifest when forebrain neurons die. Recent advances in understanding these disorders indicate that brain dysfunction precedes neurodegeneration, but the role of tau is unclear. Here, we show that early tau-related deficits develop not from the loss of synapses or neurons, but rather as a result of synaptic abnormalities caused by the accumulation of hyperphosphorylated tau within intact dendritic spines, where it disrupts synaptic function by impairing glutamate receptor trafficking or synaptic anchoring. Mutagenesis of 14 disease-associated serine and threonine amino acid residues to create pseudohyperphosphorylated tau caused tau mislocalization while creation of phosphorylation-deficient tau blocked the mis-targeting of tau to dendritic spines. Thus, tau phosphorylation plays a critical role in mediating tau mislocalization and subsequent synaptic impairment. These data establish that the locus of early synaptic malfunction caused by tau resides in dendritic spines. PMID:21172610

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. Copyright © 2015 Elsevier B.V. All rights reserved.

Mechanism of tau-induced neurodegeneration in Alzheimer disease and related tauopathies.

PubMed

Alonso, Alejandra del C; Li, Ben; Grundke-Iqbal, Inge; Iqbal, Khalid

2008-08-01

The accumulation of hyperphosphorylated tau is a common feature of several dementias. Tau is one of the brain microtubule-associated proteins. Here we discuss tau's function in microtubule assembly and stabilization and with regards to tau's interactions with other proteins, membranes, and DNA. We describe and analyze important posttranslational modifications: hyperphosphorylation, glycosylation, ubiquitination, glycation, polyamination, nitration, and truncation. We discuss how these post-translational modifications can alter tau's biological function and what is known about tau self-assembly, and we propose a mechanism of tau polymerization. We analyze the impact of natural mutations on tau that cause fronto-temporal dementia associated with chromosome 17 (FTDP-1 7). Finally, we consider whether tau accumulation or its conformational change is related to tau-induced neurodegeneration, and we propose a mechanism of neurodegeneration.

Physics of neutrino flavor transformation through matter-neutrino resonances

NASA Astrophysics Data System (ADS)

Wu, Meng-Ru; Duan, Huaiyu; Qian, Yong-Zhong

2016-01-01

In astrophysical environments such as core-collapse supernovae and neutron star-neutron star or neutron star-black hole mergers where dense neutrino media are present, matter-neutrino resonances (MNRs) can occur when the neutrino propagation potentials due to neutrino-electron and neutrino-neutrino forward scattering nearly cancel each other. We show that neutrino flavor transformation through MNRs can be explained by multiple adiabatic solutions similar to the Mikheyev-Smirnov-Wolfenstein mechanism. We find that for the normal neutrino mass hierarchy, neutrino flavor evolution through MNRs can be sensitive to the shape of neutrino spectra and the adiabaticity of the system, but such sensitivity is absent for the inverted hierarchy.

Alzheimer brain-derived tau oligomers propagate pathology from endogenous tau.

PubMed

Lasagna-Reeves, Cristian A; Castillo-Carranza, Diana L; Sengupta, Urmi; Guerrero-Munoz, Marcos J; Kiritoshi, Takaki; Neugebauer, Volker; Jackson, George R; Kayed, Rakez

2012-01-01

Intracerebral injection of brain extracts containing amyloid or tau aggregates in transgenic animals can induce cerebral amyloidosis and tau pathology. We extracted pure populations of tau oligomers directly from the cerebral cortex of Alzheimer disease (AD) brain. These oligomers are potent inhibitors of long term potentiation (LTP) in hippocampal brain slices and disrupt memory in wild type mice. We observed for the first time that these authentic brain-derived tau oligomers propagate abnormal tau conformation of endogenous murine tau after prolonged incubation. The conformation and hydrophobicity of tau oligomers play a critical role in the initiation and spread of tau pathology in the naïve host in a manner reminiscent of sporadic AD.

Increased Tau Phosphorylation and Tau Truncation, and Decreased Synaptophysin Levels in Mutant BRI2/Tau Transgenic Mice

PubMed Central

Garringer, Holly J.; Murrell, Jill; Sammeta, Neeraja; Gnezda, Anita; Ghetti, Bernardino; Vidal, Ruben

2013-01-01

Familial Danish dementia (FDD) is an autosomal dominant neurodegenerative disease caused by a 10-nucleotide duplication-insertion in the BRI2 gene. FDD is clinically characterized by loss of vision, hearing impairment, cerebellar ataxia and dementia. The main neuropathologic findings in FDD are the deposition of Danish amyloid (ADan) and the presence of neurofibrillary tangles (NFTs). Here we investigated tau accumulation and truncation in double transgenic (Tg-FDD-Tau) mice generated by crossing transgenic mice expressing human Danish mutant BRI2 (Tg-FDD) with mice expressing human 4-repeat mutant Tau-P301S (Tg-Tau). Compared to Tg-Tau mice, we observed a significant enhancement of tau deposition in Tg-FDD-Tau mice. In addition, a significant increase in tau cleaved at aspartic acid (Asp) 421 was observed in Tg-FDD-Tau mice. Tg-FDD-Tau mice also showed a significant decrease in synaptophysin levels, occurring before widespread deposition of fibrillar ADan and tau can be observed. Thus, the presence of soluble ADan/mutant BRI2 can lead to significant changes in tau metabolism and synaptic dysfunction. Our data provide new in vivo insights into the pathogenesis of FDD and the pathogenic pathway(s) by which amyloidogenic peptides, regardless of their primary amino acid sequence, can cause neurodegeneration. PMID:23418567

Increased tau phosphorylation and tau truncation, and decreased synaptophysin levels in mutant BRI2/tau transgenic mice.

PubMed

Garringer, Holly J; Murrell, Jill; Sammeta, Neeraja; Gnezda, Anita; Ghetti, Bernardino; Vidal, Ruben

2013-01-01

Familial Danish dementia (FDD) is an autosomal dominant neurodegenerative disease caused by a 10-nucleotide duplication-insertion in the BRI(2) gene. FDD is clinically characterized by loss of vision, hearing impairment, cerebellar ataxia and dementia. The main neuropathologic findings in FDD are the deposition of Danish amyloid (ADan) and the presence of neurofibrillary tangles (NFTs). Here we investigated tau accumulation and truncation in double transgenic (Tg-FDD-Tau) mice generated by crossing transgenic mice expressing human Danish mutant BRI(2) (Tg-FDD) with mice expressing human 4-repeat mutant Tau-P301S (Tg-Tau). Compared to Tg-Tau mice, we observed a significant enhancement of tau deposition in Tg-FDD-Tau mice. In addition, a significant increase in tau cleaved at aspartic acid (Asp) 421 was observed in Tg-FDD-Tau mice. Tg-FDD-Tau mice also showed a significant decrease in synaptophysin levels, occurring before widespread deposition of fibrillar ADan and tau can be observed. Thus, the presence of soluble ADan/mutant BRI(2) can lead to significant changes in tau metabolism and synaptic dysfunction. Our data provide new in vivo insights into the pathogenesis of FDD and the pathogenic pathway(s) by which amyloidogenic peptides, regardless of their primary amino acid sequence, can cause neurodegeneration.

Differential interaction and aggregation of 3-repeat and 4-repeat tau isoforms with 14-3-3{zeta} protein

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sadik, Golam; Tanaka, Toshihisa, E-mail: tanaka@psy.med.osaka-u.ac.jp; Kato, Kiyoko

2009-05-22

Tau isoforms, 3-repeat (3R) and 4-repeat tau (4R), are differentially involved in neuronal development and in several tauopathies. 14-3-3 protein binds to tau and 14-3-3/tau association has been found both in the development and in tauopathies. To understand the role of 14-3-3 in the differential regulation of tau isoforms, we have performed studies on the interaction and aggregation of 3R-tau and 4R-tau, either phosphorylated or unphosphorylated, with 14-3-3{zeta}. We show by surface plasmon resonance studies that the interaction between unphosphorylated 3R-tau and 14-3-3{zeta} is {approx}3-folds higher than that between unphosphorylated 4R-tau and 14-3-3{zeta}. Phosphorylation of tau by protein kinase Amore » (PKA) increases the affinity of both 3R- and 4R-tau for 14-3-3{zeta} to a similar level. An in vitro aggregation assay employing both transmission electron microscopy and fluorescence spectroscopy revealed the aggregation of unphosphorylated 4R-tau to be significantly higher than that of unphosphorylated 3R-tau following the induction of 14-3-3{zeta}. The filaments formed from 3R- and 4R-tau were almost similar in morphology. In contrast, the aggregation of both 3R- and 4R-tau was reduced to a similar low level after phosphorylation with PKA. Taken together, these results suggest that 14-3-3{zeta} exhibits a similar role for tau isoforms after PKA-phosphorylation, but a differential role for unphosphorylated tau. The significant aggregation of 4R-tau by 14-3-3{zeta} suggests that 14-3-3 may act as an inducer in the generation of 4R-tau-predominant neurofibrillary tangles in tauopathies.« less

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. Copyright © 2016 Elsevier Inc. All rights reserved.

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

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

PubMed

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.

Search for muon neutrino disappearance due to sterile neutrino oscillations with the MINOS/MINOS+ experiment

NASA Astrophysics Data System (ADS)

Todd, J.; Chen, R.; Huang, J.; ">MINOS, Loss of Axonal Mitochondria Promotes Tau-Mediated Neurodegeneration and Alzheimer's Disease–Related Tau Phosphorylation Via PAR-1

PubMed Central

Iijima-Ando, Kanae; Sekiya, Michiko; Suzuki, Emiko; Lu, Bingwei; Iijima, Koichi M.

2012-01-01

Abnormal phosphorylation and toxicity of a microtubule-associated protein tau are involved in the pathogenesis of Alzheimer's disease (AD); however, what pathological conditions trigger tau abnormality in AD is not fully understood. A reduction in the number of mitochondria in the axon has been implicated in AD. In this study, we investigated whether and how loss of axonal mitochondria promotes tau phosphorylation and toxicity in vivo. Using transgenic Drosophila expressing human tau, we found that RNAi–mediated knockdown of milton or Miro, an adaptor protein essential for axonal transport of mitochondria, enhanced human tau-induced neurodegeneration. Tau phosphorylation at an AD–related site Ser262 increased with knockdown of milton or Miro; and partitioning defective-1 (PAR-1), the Drosophila homolog of mammalian microtubule affinity-regulating kinase, mediated this increase of tau phosphorylation. Tau phosphorylation at Ser262 has been reported to promote tau detachment from microtubules, and we found that the levels of microtubule-unbound free tau increased by milton knockdown. Blocking tau phosphorylation at Ser262 site by PAR-1 knockdown or by mutating the Ser262 site to unphosphorylatable alanine suppressed the enhancement of tau-induced neurodegeneration caused by milton knockdown. Furthermore, knockdown of milton or Miro increased the levels of active PAR-1. These results suggest that an increase in tau phosphorylation at Ser262 through PAR-1 contributes to tau-mediated neurodegeneration under a pathological condition in which axonal mitochondria is depleted. Intriguingly, we found that knockdown of milton or Miro alone caused late-onset neurodegeneration in the fly brain, and this neurodegeneration could be suppressed by knockdown of Drosophila tau or PAR-1. Our results suggest that loss of axonal mitochondria may play an important role in tau phosphorylation and toxicity in the pathogenesis of AD. PMID:22952452

Interaction of tau protein with model lipid membranes induces tau structural compaction and membrane disruption

PubMed Central

Jones, Emmalee M.; Dubey, Manish; Camp, Phillip J.; Vernon, Briana C.; Biernat, Jacek; Mandelkow, Eckhard; Majewski, Jaroslaw; Chi, Eva Y.

2012-01-01

The misfolding and aggregation of the intrinsically disordered, microtubule-associated tau protein into neurofibrillary tangles is implicated in the pathogenesis of Alzheimer's disease. However, the mechanisms of tau aggregation and toxicity remain unknown. Recent work has shown that lipid membrane can induce tau aggregation and that membrane permeabilization may serve as a pathway by which protein aggregates exert toxicity, suggesting that the plasma membrane may play dual roles in tau pathology. This prompted our investigation to assess tau's propensity to interact with membranes and to elucidate the mutually disruptive structural perturbations the interactions induce in both tau and the membrane. We show that although highly charged and soluble, the full-length tau (hTau40) is also highly surface active, selectively inserts into anionic DMPG lipid monolayers and induces membrane morphological changes. To resolve molecular-scale structural details of hTau40 associated with lipid membranes, X-ray and neutron scattering techniques are utilized. X-ray reflectivity indicates hTau40's presence underneath a DMPG monolayer and penetration into the lipid headgroups and tailgroups, whereas grazing incidence X-ray diffraction shows that hTau40 insertion disrupts lipid packing. Moreover, both air/water and DMPG lipid membrane interfaces induce the disordered hTau40 to partially adopt a more compact conformation with density similar to that of a folded protein. Neutron reflectivity shows that tau completely disrupts supported DMPG bilayers while leaving the neutral DPPC bilayer intact. Our results show that hTau40's strong interaction with anionic lipids induces tau structural compaction and membrane disruption, suggesting possible membrane-based mechanisms of tau aggregation and toxicity in neurodegenerative diseases. PMID:22401494

Analysis of tau post-translational modifications in rTg4510 mice, a model of tau pathology.

PubMed

Song, Lixin; Lu, Sherry X; Ouyang, Xuesong; Melchor, Jerry; Lee, Julie; Terracina, Giuseppe; Wang, Xiaohai; Hyde, Lynn; Hess, J Fred; Parker, Eric M; Zhang, Lili

2015-03-26

Microtubule associated protein tau is the major component of the neurofibrillary tangles (NFTs) found in the brains of patients with Alzheimer's disease and several other neurodegenerative diseases. Tau mutations are associated with frontotemperal dementia with parkinsonism on chromosome 17 (FTDP-17). rTg4510 mice overexpress human tau carrying the P301L FTDP-17 mutation and develop robust NFT-like pathology at 4-5 months of age. The current study is aimed at characterizing the rTg4510 mice to better understand the genesis of tau pathology and to better enable the use of this model in drug discovery efforts targeting tau pathology. Using a panel of immunoassays, we analyzed the age-dependent formation of pathological tau in rTg4510 mice and our data revealed a steady age-dependent accumulation of pathological tau in the insoluble fraction of brain homogenates. The pathological tau was associated with multiple post-translational modifications including aggregation, phosphorylation at a wide variety of sites, acetylation, ubiquitination and nitration. The change of most tau species reached statistical significance at the age of 16 weeks. There was a strong correlation between the different post-translationally modified tau species in this heterogeneous pool of pathological tau. Total tau in the cerebrospinal fluid (CSF) displayed a multiphasic temporal profile distinct from the steady accumulation of pathological tau in the brain. Female rTg4510 mice displayed significantly more aggressive accumulation of pathological tau in the brain and elevation of total tau in CSF than their male littermates. The immunoassays described here were used to generate the most comprehensive description of the changes in various tau species across the lifespan of the rTg4510 mouse model. The data indicate that development of tauopathy in rTg4510 mice involves the accumulation of a pool of pathological tau that carries multiple post-translational modifications, a process that can be detected well before the histological detection of NFTs. Therapeutic treatment targeting tau should therefore aim to reduce all tau species associated with the pathological tau pool rather than reduce specific post-translational modifications. There is still much to learn about CSF tau in physiological and pathological processes in order to use it as a translational biomarker in drug discovery.

Neurodegenerative disorder FTDP-17-related tau intron 10 +16C → T mutation increases tau exon 10 splicing and causes tauopathy in transgenic mice.

PubMed

Umeda, Tomohiro; Yamashita, Takenari; Kimura, Tetsuya; Ohnishi, Kiyouhisa; Takuma, Hiroshi; Ozeki, Tomoko; Takashima, Akihiko; Tomiyama, Takami; Mori, Hiroshi

2013-07-01

Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) is a neurodegenerative disorder caused by mutations in the tau gene. Many mutations identified in FTDP-17 have been shown to affect tau exon 10 splicing in vitro, which presumably causes pathologic imbalances in exon 10(-) [3-repeat (3R)] and exon 10(+) [4-repeat (4R)] tau expression and leads to intracellular inclusions of hyperphosphorylated tau in patient brains. However, no reports have investigated this theory using model mice with a tau intronic mutation. Herein, we generated new transgenic mice harboring the tau intron 10 +16C → T mutation. We prepared a transgene construct containing intronic sequences required for exon 10 splicing in the longest tau isoform cDNA. Although mice bearing the construct without the intronic mutation showed normal developmental changes of the tau isoform from 3R tau to equal amounts of 3R and 4R tau, mice with the mutation showed much higher levels of 4R tau at the adult stage. 4R tau was selectively recovered in insoluble brain fractions in their old age. Furthermore, these mice displayed abnormal tau phosphorylation, synapse loss and dysfunction, memory impairment, glial activation, tangle formation, and neuronal loss in an age-dependent manner. These findings provide the first evidence in a mouse model that a tau intronic mutation-induced imbalance of 3R and 4R tau could be a cause of tauopathy. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Comparing Plasma Phospho Tau, Total Tau, and Phospho Tau–Total Tau Ratio as Acute and Chronic Traumatic Brain Injury Biomarkers

PubMed Central

Rubenstein, Richard; Chang, Binggong; Yue, John K.; Chiu, Allen; Winkler, Ethan A.; Puccio, Ava M.; Diaz-Arrastia, Ramon; Yuh, Esther L.; Mukherjee, Pratik; Valadka, Alex B.; Gordon, Wayne A.; Okonkwo, David O.; Davies, Peter; Agarwal, Sanjeev; Lin, Fan; Sarkis, George; Yadikar, Hamad; Yang, Zhihui; Manley, Geoffrey T.; Wang, Kevin K. W.

2017-01-01

IMPORTANCE Annually in the United States, at least 3.5 million people seek medical attention for traumatic brain injury (TBI). The development of therapies for TBI is limited by the absence of diagnostic and prognostic biomarkers. Microtubule-associated protein tau is an axonal phosphoprotein. To date, the presence of the hypophosphorylated tau protein (P-tau) in plasma from patients with acute TBI and chronic TBI has not been investigated. OBJECTIVE To examine the associations between plasma P-tau and total-tau (T-tau) levels and injury presence, severity, type of pathoanatomic lesion (neuroimaging), and patient outcomes in acute and chronic TBI. DESIGN, SETTING, AND PARTICIPANTS In the TRACK-TBI Pilot study, plasma was collected at a single time point from 196 patients with acute TBI admitted to 3 level I trauma centers (<24 hours after injury) and 21 patients with TBI admitted to inpatient rehabilitation units (mean [SD], 176.4 [44.5] days after injury). Control samples were purchased from a commercial vendor. The TRACK-TBI Pilot study was conducted from April 1, 2010, to June 30, 2012. Data analysis for the current investigation was performed from August 1, 2015, to March 13, 2017. MAIN OUTCOMES AND MEASURES Plasma samples were assayed for P-tau (using an antibody that specifically recognizes phosphothreonine-231) and T-tau using ultra-high sensitivity laser-based immunoassay multi-arrayed fiberoptics conjugated with rolling circle amplification. RESULTS In the 217 patients with TBI, 161 (74.2%) were men; mean (SD) age was 42.5 (18.1) years. The P-tau and T-tau levels and P-tau–T-tau ratio in patients with acute TBI were higher than those in healthy controls. Receiver operating characteristic analysis for the 3 tau indices demonstrated accuracy with area under the curve (AUC) of 1.000, 0.916, and 1.000, respectively, for discriminating mild TBI (Glasgow Coma Scale [GCS] score, 13–15, n = 162) from healthy controls. The P-tau level and P-tau–T-tau ratio were higher in individuals with more severe TBI (GCS, ≤12 vs 13–15). The P-tau level and P-tau–T-tau ratio outperformed the T-tau level in distinguishing cranial computed tomography–positive from −negative cases (AUC = 0.921, 0.923, and 0.646, respectively). Acute P-tau levels and P-tau–T-tau ratio weakly distinguished patients with TBI who had good outcomes (Glasgow Outcome Scale–Extended GOS-E, 7–8) (AUC = 0.663 and 0.658, respectively) and identified those with poor outcomes (GOS-E, ≤4 vs >4) (AUC = 0.771 and 0.777, respectively). Plasma samples from patients with chronic TBI also showed elevated P-tau levels and a P-tau–T-tau ratio significantly higher than that of healthy controls, with both P-tau indices strongly discriminating patients with chronic TBI from healthy controls (AUC = 1.000 and 0.963, respectively). CONCLUSIONS AND RELEVANCE Plasma P-tau levels and P-tau–T-tau ratio outperformed T-tau level as diagnostic and prognostic biomarkers for acute TBI. Compared with T-tau levels alone, P-tau levels and P-tau–T-tau ratios show more robust and sustained elevations among patients with chronic TBI. PMID:28738126

Acquiring information about neutrino parameters by detecting supernova neutrinos

NASA Astrophysics Data System (ADS)

Huang, Ming-Yang; Guo, Xin-Heng; Young, Bing-Lin

2010-08-01

We consider the supernova shock effects, the Mikheyev-Smirnov-Wolfenstein effects, the collective effects, and the Earth matter effects in the detection of type II supernova neutrinos on the Earth. It is found that the event number of supernova neutrinos depends on the neutrino mass hierarchy, the neutrino mixing angle θ13, and neutrino masses. Therefore, we propose possible methods to identify the mass hierarchy and acquire information about θ13 and neutrino masses by detecting supernova neutrinos. We apply these methods to some current neutrino experiments.

Astroparticle physics with solar neutrinos

PubMed Central

NAKAHATA, Masayuki

2011-01-01

Solar neutrino experiments observed fluxes smaller than the expectations from the standard solar model. This discrepancy is known as the “solar neutrino problem”. Flux measurements by Super-Kamiokande and SNO have demonstrated that the solar neutrino problem is due to neutrino oscillations. Combining the results of all solar neutrino experiments, parameters for solar neutrino oscillations are obtained. Correcting for the effect of neutrino oscillations, the observed neutrino fluxes are consistent with the prediction from the standard solar model. In this article, results of solar neutrino experiments are reviewed with detailed descriptions of what Kamiokande and Super-Kamiokande have contributed to the history of astroparticle physics with solar neutrino measurements. PMID:21558758

Los Alamos Science, Number 25 -- 1997: Celebrating the Neutrino

DOE R&D Accomplishments Database

Cooper, N. G. ed.

1997-01-01

This issue is devoted to the neutrino and its remaining mysteries. It is divided into the following areas: (1) The Reines-Cowan experiment -- detecting the poltergeist; (2) The oscillating neutrino -- an introduction to neutrino masses and mixing; (3) A brief history of neutrino experiments at LAMPF; (4) A thousand eyes -- the story of LSND (Los Alamos neutrino oscillation experiment); (5) The evidence for oscillations; (6) The nature of neutrinos in muon decay and physics beyond the Standard Model; (7) Exorcising ghosts -- in pursuit of the missing solar neutrinos; (8) MSW -- a possible solution to the solar neutrino problem; (8) Neutrinos and supernovae; and (9) Dark matter and massive neutrinos.

Structure-based inhibitors of tau aggregation

NASA Astrophysics Data System (ADS)

Seidler, P. M.; Boyer, D. R.; Rodriguez, J. A.; Sawaya, M. R.; Cascio, D.; Murray, K.; Gonen, T.; Eisenberg, D. S.

2018-02-01

Aggregated tau protein is associated with over 20 neurological disorders, which include Alzheimer's disease. Previous work has shown that tau's sequence segments VQIINK and VQIVYK drive its aggregation, but inhibitors based on the structure of the VQIVYK segment only partially inhibit full-length tau aggregation and are ineffective at inhibiting seeding by full-length fibrils. Here we show that the VQIINK segment is the more powerful driver of tau aggregation. Two structures of this segment determined by the cryo-electron microscopy method micro-electron diffraction explain its dominant influence on tau aggregation. Of practical significance, the structures lead to the design of inhibitors that not only inhibit tau aggregation but also inhibit the ability of exogenous full-length tau fibrils to seed intracellular tau in HEK293 biosensor cells into amyloid. We also raise the possibility that the two VQIINK structures represent amyloid polymorphs of tau that may account for a subset of prion-like strains of tau.

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

PubMed Central

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

Azaphilones inhibit tau aggregation and dissolve tau aggregates in vitro.

PubMed

Paranjape, Smita R; Riley, Andrew P; Somoza, Amber D; Oakley, C Elizabeth; Wang, Clay C C; Prisinzano, Thomas E; Oakley, Berl R; Gamblin, T Chris

2015-05-20

The aggregation of the microtubule-associated protein tau is a seminal event in many neurodegenerative diseases, including Alzheimer's disease. The inhibition or reversal of tau aggregation is therefore a potential therapeutic strategy for these diseases. Fungal natural products have proven to be a rich source of useful compounds having wide varieties of biological activities. We have previously screened Aspergillus nidulans secondary metabolites for their ability to inhibit tau aggregation in vitro using an arachidonic acid polymerization protocol. One aggregation inhibitor identified was asperbenzaldehyde, an intermediate in azaphilone biosynthesis. We therefore tested 11 azaphilone derivatives to determine their tau assembly inhibition properties in vitro. All compounds tested inhibited tau filament assembly to some extent, and four of the 11 compounds had the advantageous property of disassembling preformed tau aggregates in a dose-dependent fashion. The addition of these compounds to the tau aggregates reduced both the total length and number of tau polymers. The most potent compounds were tested in in vitro reactions to determine whether they interfere with tau's normal function of stabilizing microtubules (MTs). We found that they did not completely inhibit MT assembly in the presence of tau. These derivatives are very promising lead compounds for tau aggregation inhibitors and, more excitingly, for compounds that can disassemble pre-existing tau filaments. They also represent a new class of anti-tau aggregation compounds with a novel structural scaffold.

Tau Fibril Formation in Cultured Cells Compatible with a Mouse Model of Tauopathy.

PubMed

Matsumoto, Gen; Matsumoto, Kazuki; Kimura, Taeko; Suhara, Tetsuya; Higuchi, Makoto; Sahara, Naruhiko; Mori, Nozomu

2018-05-17

Neurofibrillary tangles composed of hyperphosphorylated tau protein are primarily neuropathological features of a number of neurodegenerative diseases collectively termed tauopathy. To understand the mechanisms underlying the cause of tauopathy, precise cellular and animal models are required. Recent data suggest that the transient introduction of exogenous tau can accelerate the development of tauopathy in the brains of non-transgenic and transgenic mice expressing wild-type human tau. However, the transmission mechanism leading to tauopathy is not fully understood. In this study, we developed cultured-cell models of tauopathy representing a human tauopathy. Neuro2a (N2a) cells containing propagative tau filaments were generated by introducing purified tau fibrils. These cell lines expressed full-length (2N4R) human tau and the green fluorescent protein (GFP)-fused repeat domain of tau with P301L mutation. Immunocytochemistry and super-resolution microscopic imaging revealed that tau inclusions exhibited filamentous morphology and were composed of both full-length and repeat domain fragment tau. Live-cell imaging analysis revealed that filamentous tau inclusions are transmitted to daughter cells, resulting in yeast-prion-like propagation. By a standard method of tau preparation, both full-length tau and repeat domain fragments were recovered in sarkosyl insoluble fraction. Hyperphosphorylation of full-length tau was confirmed by the immunoreactivity of phospho-Tau antibodies and mobility shifts by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). These properties were similar to the biochemical features of P301L mutated human tau in a mouse model of tauopathy. In addition, filamentous tau aggregates in cells barely co-localized with ubiquitins, suggesting that most tau aggregates were excluded from protein degradation systems, and thus propagated to daughter cells. The present cellular model of tauopathy will provide an advantage for dissecting the mechanisms of tau aggregation and degradation and be a powerful tool for drug screening to prevent tauopathy.

Search for the lepton-flavor-violating leptonic B(0)-->mu(+/-)tau(-/+) and B(0)-->e(+/-)tau(-/+).

PubMed

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

2004-12-10

We have searched a sample of 9.6 x 10(6) BB events for the lepton-flavor-violating leptonic B decays, B(0)-->mu(+/-)tau(-/+) and B(0)-->e(+/-)tau(-/+). The tau lepton was detected through the decay modes tau-->lnunu(-) , where l=e, mu. There is no indication of a signal, and we obtain the 90% confidence level upper limits B(B(0)-->mu(+/-)tau(-/+))<3.8 x 10(-5) and B(B(0)-->e(+/-)tau(-/+))<1.3 x 10(-4).

Neutrino Oscillations and the Sudbury Neutrino Observatory

NASA Astrophysics Data System (ADS)

Wark, David

2001-04-01

When the existence of the neutrino was almost apologetically first proposed by Wolfgang Pauli it was intended to explain the mysterious apparent absence of energy and momentum in beta decay. 70 years later the neutrino has indeed solved that mystery, but it has generated still more of its own. Are neutrinos massive? Is it possible to create a neutrino with its spin in the same direction as its momentum? What fraction of the mass of the Universe is made up of neutrinos? Are the flavour labels which we put on neutrinos, like electron and muon, really fixed or can they change? Why does no experiment see the predicted flux of neutrinos from the Sun? Why do there appear to be roughly equal numbers of muon and electron neutrinos created in our atmosphere, rather than the 2:1 ratio we would expect? Many of these questions were coupled when Bruno Pontecorvo first suggested that the shortfall in solar neutrino measurements were caused by neutrino oscillations - neutrinos spontaneously changing flavour as they travel from the Sun. 30 years later we still await definitive proof of that conjecture, and providing that proof is the reason for the Sudbury Neutrino Observatory. The talk will discuss the current state of neutrino oscillations studies, and show how the unique capabilities of the Sudbury Neutrino Observatory can provide definitive proof of whether neutrino oscillations are the long-sought answer to the solar neutrino problem.

Neutrino Physics at Drexel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lane, Charles; Dolinski, Michelle; Neilson, Russell

Our primary goal is to improve the understanding of the properties and interactions of neutrinos. We are pursuing this by means of the DUNE long-baseline and PROSPECT short-baseline neutrino experiments. For DUNE, a neutrino beam from Fermilab will be detected at the SURF facility in South Dakota, with the aim of determining the neutrino mass hierarchy (the mass ordering of neutrino flavors), and a measurement or limit on CP-violation via neutrinos. Our near-term experimental goal is to improve the characterization of the neutrino beam by measurements of muons produced as a byproduct of neutrino beam generation, to quantify the beammore » composition and flux. The short-range neutrino program has the aim of using the HFIR reactor at Oak Ridge as a neutrino source, with a detector placed nearby to find if there are short-distance oscillations to sterile neutrino flavors, and to resolve the 'reactor neutrino spectral anomaly' which has shown up as an unexplained 'bump' in the neutrino energy spectrum in recent experiments.« less

REVIEWS OF TOPICAL PROBLEMS: The neutrino mass in elementary-particle physics and in big bang cosmology

NASA Astrophysics Data System (ADS)

Zel'dovich, Ya B.; Khlopov, M. Yu

1981-09-01

Some theoretical aspects of a nonzero value for the neutrino rest mass and its possible implications for physics are discussed. The nature of the neutrino mass is analyzed, as well as the physical consequences that may derive from the existence of new helicity states for the neutrino or from lepton charge nonconservation if the mass is of Dirac or Majorana character, respectively. Massive neutrinos are examined in the context of grand unified theories combining the weak, strong, and electromagnetic interactions. Searches for neutrino-mass effects in β decay and for neutrino oscillations are reviewed. Several astrophysical effects of the neutrino mass are described: solar-neutrino oscillations, the decay of primordial neutrinos, the feasibility of detecting massive primordial neutrinos experimentally. The predictions of big bang theory regarding the neutrino number density in the universe are analyzed, and a discussion is given of the influence neutrino oscillations might have on the neutrino density and on cosmological nucleosynthesis.

Shower disc sampling and the angular resolution of gamma-ray shower detectors

NASA Technical Reports Server (NTRS)

Lambert, A.; Lloyd-Evans, J.

1985-01-01

As part of the design study for the new UHE gamma ray detector being constsructed at Haverah Park, a series of experiments using scintillators operated side-by-side in 10 to the 15th power eV air showers are undertaken. Investigation of the rms sampling fluctuations in the shower disc arrival time yields an upper limit to the intrinsic sampling uncertainty, sigma sub rms = (1.1 + or - 0.1)ns, implying an angular resolution capability 1 deg for an inter-detector spacing of approximately 25 m.

TeV radiation from the Crab nebula and other matters

NASA Technical Reports Server (NTRS)

Lamb, R. C.

1990-01-01

The detection of the Crab Nebula via the Cherenkov imaging technique places TeV astronomy on a secure observational footing. The motivation for TeV observations, a discussion of the atmospheric Cherenkov technique, the experimental details of the Crab Nebula detection, and its scientific implications are presented. The present dilemma of VHE/UHE astronomy is that the Crab appears to be the only source whose showers match theoretical expectations. The situation will be clarified as improved ground-based detectors come on-line with sensitivities matching those of the GRO (Gamma Ray Observatory) instruments.

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

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

Astroparticle physics with solar neutrinos.

PubMed

Nakahata, Masayuki

2011-01-01

Solar neutrino experiments observed fluxes smaller than the expectations from the standard solar model. This discrepancy is known as the "solar neutrino problem". Flux measurements by Super-Kamiokande and SNO have demonstrated that the solar neutrino problem is due to neutrino oscillations. Combining the results of all solar neutrino experiments, parameters for solar neutrino oscillations are obtained. Correcting for the effect of neutrino oscillations, the observed neutrino fluxes are consistent with the prediction from the standard solar model. In this article, results of solar neutrino experiments are reviewed with detailed descriptions of what Kamiokande and Super-Kamiokande have contributed to the history of astroparticle physics with solar neutrino measurements. (Communicated by Toshimitsu Yamazaki, M.J.A.).

Los Alamos Science, Number 25 -- 1997: Celebrating the neutrino

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cooper, N.G.

1997-12-31

This issue is devoted to the neutrino and its remaining mysteries. It is divided into the following areas: (1) The Reines-Cowan experiment -- detecting the poltergeist; (2) The oscillating neutrino -- an introduction to neutrino masses and mixing; (3) A brief history of neutrino experiments at LAMPF; (4) A thousand eyes -- the story of LSND (Los Alamos neutrino oscillation experiment); (5) The evidence for oscillations; (6) The nature of neutrinos in muon decay and physics beyond the Standard Model; (7) Exorcising ghosts -- in pursuit of the missing solar neutrinos; (8) MSW -- a possible solution to the solarmore » neutrino problem; (8) Neutrinos and supernovae; and (9) Dark matter and massive neutrinos.« less

The toxicity of tau in Alzheimer disease: turnover, targets and potential therapeutics.

PubMed

Pritchard, Susanne M; Dolan, Philip J; Vitkus, Alisa; Johnson, Gail V W

2011-08-01

It has been almost 25 years since the initial discovery that tau was the primary component of the neurofibrillary tangles (NFTs) in Alzheimer disease (AD) brain. Although AD is defined by both β-amyloid (Aβ) pathology (Aβ plaques) and tau pathology (NFTs), whether or not tau played a critical role in disease pathogenesis was a subject of discussion for many years. However, given the increasing evidence that pathological forms of tau can compromise neuronal function and that tau is likely an important mediator of Aβ toxicity, there is a growing awareness that tau is a central player in AD pathogenesis. In this review we begin with a brief history of tau, then provide an overview of pathological forms of tau, followed by a discussion of the differential degradation of tau by either the proteasome or autophagy and possible mechanisms by which pathological forms of tau may exert their toxicity. We conclude by discussing possible avenues for therapeutic intervention based on these emerging themes of tau's role in AD. © 2011 The Authors Journal compilation © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

Lysine-Directed Post-translational Modifications of Tau Protein in Alzheimer's Disease and Related Tauopathies

PubMed Central

Kontaxi, Christiana; Piccardo, Pedro; Gill, Andrew C.

2017-01-01

Tau is a microtubule-associated protein responsible mainly for stabilizing the neuronal microtubule network in the brain. Under normal conditions, tau is highly soluble and adopts an “unfolded” conformation. However, it undergoes conformational changes resulting in a less soluble form with weakened microtubule stabilizing properties. Altered tau forms characteristic pathogenic inclusions in Alzheimer's disease and related tauopathies. Although, tau hyperphosphorylation is widely considered to be the major trigger of tau malfunction, tau undergoes several post-translational modifications at lysine residues including acetylation, methylation, ubiquitylation, SUMOylation, and glycation. We are only beginning to define the site-specific impact of each type of lysine modification on tau biology as well as the possible interplay between them, but, like phosphorylation, these modifications are likely to play critical roles in tau's normal and pathobiology. This review summarizes the latest findings focusing on lysine post-translational modifications that occur at both endogenous tau protein and pathological tau forms in AD and other tauopathies. In addition, it highlights the significance of a site-dependent approach of studying tau post-translational modifications under normal and pathological conditions. PMID:28848737

Secretion of full-length Tau or Tau fragments in cell culture models. Propagation of Tau in vivo and in vitro.

PubMed

Pérez, Mar; Medina, Miguel; Hernández, Félix; Avila, Jesús

2018-03-05

The microtubule-associated protein Tau plays a crucial role in stabilizing neuronal microtubules. In Tauopathies, Tau loses its ability to bind microtubules, detach from them and forms intracellular aggregates. Increasing evidence in recent years supports the notion that Tau pathology spreading throughout the brain in AD and other Tauopathies is the consequence of the propagation of specific Tau species along neuroanatomically connected brain regions in a so-called "prion-like" manner. A number of steps are assumed to be involved in this process, including secretion, cellular uptake, transcellular transfer and/or seeding, although the precise mechanisms underlying propagation of Tau pathology are not fully understood yet. This review summarizes recent evidence on the nature of the specific Tau species that are propagated and the different mechanisms of Tau pathology spreading.

Oscillation properties of active and sterile neutrinos and neutrino anomalies at short distances

DOE Office of Scientific and Technical Information (OSTI.GOV)

Khruschov, V. V., E-mail: khruschov-vv@nrcki.ru; Fomichev, S. V., E-mail: fomichev-sv@nrcki.ru; Titov, O. A., E-mail: titov-oa@nrcki.ru

2016-09-15

A generalized phenomenological (3 + 2 + 1) model featuring three active and three sterile neutrinos that is intended for calculating oscillation properties of neutrinos for the case of a normal active neutrino mass hierarchy and a large splitting between the mass of one sterile neutrino and the masses of the other two sterile neutrinos is considered. A new parametrization and a specific form of the general mixing matrix are proposed for active and sterile neutrinos with allowance for possible CP violation in the lepton sector, and test values are chosen for the neutrino masses and mixing parameters. The probabilitiesmore » for the transitions between different neutrino flavors are calculated, and graphs representing the probabilities for the disappearance of muon neutrinos/antineutrinos and the appearance of electron neutrinos/antineutrinos in a beam of muon neutrinos/antineutrinos versus the distance from the neutrino source for various values of admissible model parameters at neutrino energies not higher than 50 MeV, as well as versus the ratio of this distance to the neutrino energy, are plotted. It is shown that the short-distance accelerator anomaly in neutrino data (LNSD anomaly) can be explained in the case of a specific mixing matrix for active and sterile neutrinos (which belongs to the a{sub 2} type) at the chosen parameter values. The same applies to the short-distance reactor and gallium anomalies. The theoretical results obtained in the present study can be used to interpret and predict the results of ground-based neutrino experiments aimed at searches for sterile neutrinos, as well as to analyze some astrophysical observational data.« less

Treatment-as-usual (TAU) is anything but usual: a meta-analysis of CBT versus TAU for anxiety and depression.

PubMed

Watts, Sarah E; Turnell, Adrienne; Kladnitski, Natalie; Newby, Jill M; Andrews, Gavin

2015-04-01

There were three aims of this study, the first was to examine the efficacy of CBT versus treatment-as-usual (TAU) in the treatment of anxiety and depressive disorders, the second was to examine how TAU is defined in TAU control groups for those disorders, and the third was to explore whether the type of TAU condition influences the estimate of effects of CBT. A systematic search of Cochrane Central Register of Controlled Trials, PsycINFO, and CINAHL was conducted. 48 studies of CBT for depressive or anxiety disorders (n=6926) that specified that their control group received TAU were identified. Most (n=45/48) provided an explanation of the TAU group however there was significant heterogeneity amongst TAU conditions. The meta-analysis showed medium effects favoring CBT over TAU for both anxiety (g=0.69, 95% CI 0.47-0.92, p<0.001, n=1318) and depression (g=0.70, 95% CI 0.49-0.90, p<0.001, n=5054), with differential effects observed across TAU conditions. CBT is superior to TAU and the size of the effect of CBT compared to TAU depends on the nature of the TAU condition. The term TAU is used in different ways and should be more precisely described. The four key details to be reported can be thought of as "who, what, how many, and any additional treatments?" Copyright © 2014 Elsevier B.V. All rights reserved.

Oscillation properties of active and sterile neutrinos and neutrino anomalies at short distances

NASA Astrophysics Data System (ADS)

Khruschov, V. V.; Fomichev, S. V.; Titov, O. A.

2016-09-01

A generalized phenomenological (3 + 2 + 1) model featuring three active and three sterile neutrinos that is intended for calculating oscillation properties of neutrinos for the case of a normal activeneutrino mass hierarchy and a large splitting between the mass of one sterile neutrino and the masses of the other two sterile neutrinos is considered. A new parametrization and a specific form of the general mixing matrix are proposed for active and sterile neutrinos with allowance for possible CP violation in the lepton sector, and test values are chosen for the neutrino masses and mixing parameters. The probabilities for the transitions between different neutrino flavors are calculated, and graphs representing the probabilities for the disappearance of muon neutrinos/antineutrinos and the appearance of electron neutrinos/antineutrinos in a beam of muon neutrinos/antineutrinos versus the distance from the neutrino source for various values of admissible model parameters at neutrino energies not higher than 50 MeV, as well as versus the ratio of this distance to the neutrino energy, are plotted. It is shown that the short-distance accelerator anomaly in neutrino data (LNSD anomaly) can be explained in the case of a specific mixing matrix for active and sterile neutrinos (which belongs to the a 2 type) at the chosen parameter values. The same applies to the short-distance reactor and gallium anomalies. The theoretical results obtained in the present study can be used to interpret and predict the results of ground-based neutrino experiments aimed at searches for sterile neutrinos, as well as to analyze some astrophysical observational data.

Tauopathy induced by low level expression of a human brain-derived tau fragment in mice is rescued by phenylbutyrate.

PubMed

Bondulich, Marie K; Guo, Tong; Meehan, Christopher; Manion, John; Rodriguez Martin, Teresa; Mitchell, Jacqueline C; Hortobagyi, Tibor; Yankova, Natalia; Stygelbout, Virginie; Brion, Jean-Pierre; Noble, Wendy; Hanger, Diane P

2016-08-01

Human neurodegenerative tauopathies exhibit pathological tau aggregates in the brain along with diverse clinical features including cognitive and motor dysfunction. Post-translational modifications including phosphorylation, ubiquitination and truncation, are characteristic features of tau present in the brain in human tauopathy. We have previously reported an N-terminally truncated form of tau in human brain that is associated with the development of tauopathy and is highly phosphorylated. We have generated a new mouse model of tauopathy in which this human brain-derived, 35 kDa tau fragment (Tau35) is expressed in the absence of any mutation and under the control of the human tau promoter. Most existing mouse models of tauopathy overexpress mutant tau at levels that do not occur in human neurodegenerative disease, whereas Tau35 transgene expression is equivalent to less than 10% of that of endogenous mouse tau. Tau35 mice recapitulate key features of human tauopathies, including aggregated and abnormally phosphorylated tau, progressive cognitive and motor deficits, autophagic/lysosomal dysfunction, loss of synaptic protein, and reduced life-span. Importantly, we found that sodium 4-phenylbutyrate (Buphenyl®), a drug used to treat urea cycle disorders and currently in clinical trials for a range of neurodegenerative diseases, reverses the observed abnormalities in tau and autophagy, behavioural deficits, and loss of synapsin 1 in Tau35 mice. Our results show for the first time that, unlike other tau transgenic mouse models, minimal expression of a human disease-associated tau fragment in Tau35 mice causes a profound and progressive tauopathy and cognitive changes, which are rescued by pharmacological intervention using a clinically approved drug. These novel Tau35 mice therefore represent a highly disease-relevant animal model in which to investigate molecular mechanisms and to develop novel treatments for human tauopathies. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.

Tauopathy induced by low level expression of a human brain-derived tau fragment in mice is rescued by phenylbutyrate

PubMed Central

Bondulich, Marie K.; Guo, Tong; Meehan, Christopher; Manion, John; Rodriguez Martin, Teresa; Mitchell, Jacqueline C.; Hortobagyi, Tibor; Yankova, Natalia; Stygelbout, Virginie; Brion, Jean-Pierre; Noble, Wendy

2016-01-01

Abstract Human neurodegenerative tauopathies exhibit pathological tau aggregates in the brain along with diverse clinical features including cognitive and motor dysfunction. Post-translational modifications including phosphorylation, ubiquitination and truncation, are characteristic features of tau present in the brain in human tauopathy. We have previously reported an N-terminally truncated form of tau in human brain that is associated with the development of tauopathy and is highly phosphorylated. We have generated a new mouse model of tauopathy in which this human brain-derived, 35 kDa tau fragment (Tau35) is expressed in the absence of any mutation and under the control of the human tau promoter. Most existing mouse models of tauopathy overexpress mutant tau at levels that do not occur in human neurodegenerative disease, whereas Tau35 transgene expression is equivalent to less than 10% of that of endogenous mouse tau. Tau35 mice recapitulate key features of human tauopathies, including aggregated and abnormally phosphorylated tau, progressive cognitive and motor deficits, autophagic/lysosomal dysfunction, loss of synaptic protein, and reduced life-span. Importantly, we found that sodium 4-phenylbutyrate (Buphenyl®), a drug used to treat urea cycle disorders and currently in clinical trials for a range of neurodegenerative diseases, reverses the observed abnormalities in tau and autophagy, behavioural deficits, and loss of synapsin 1 in Tau35 mice. Our results show for the first time that, unlike other tau transgenic mouse models, minimal expression of a human disease-associated tau fragment in Tau35 mice causes a profound and progressive tauopathy and cognitive changes, which are rescued by pharmacological intervention using a clinically approved drug. These novel Tau35 mice therefore represent a highly disease-relevant animal model in which to investigate molecular mechanisms and to develop novel treatments for human tauopathies. PMID:27297240

Neutrino Oscillations within the Induced Gravitational Collapse Paradigm of Long Gamma-Ray Bursts

NASA Astrophysics Data System (ADS)

Becerra, L.; Guzzo, M. M.; Rossi-Torres, F.; Rueda, J. A.; Ruffini, R.; Uribe, J. D.

2018-01-01

The induced gravitational collapse paradigm of long gamma-ray bursts associated with supernovae (SNe) predicts a copious neutrino–antineutrino (ν \\bar{ν }) emission owing to the hypercritical accretion process of SN ejecta onto a neutron star (NS) binary companion. The neutrino emission can reach luminosities of up to 1057 MeV s‑1, mean neutrino energies of 20 MeV, and neutrino densities of 1031 cm‑3. Along their path from the vicinity of the NS surface outward, such neutrinos experience flavor transformations dictated by the neutrino-to-electron-density ratio. We determine the neutrino and electron on the accretion zone and use them to compute the neutrino flavor evolution. For normal and inverted neutrino mass hierarchies and within the two-flavor formalism ({ν }e{ν }x), we estimate the final electronic and nonelectronic neutrino content after two oscillation processes: (1) neutrino collective effects due to neutrino self-interactions where the neutrino density dominates, and (2) the Mikheyev–Smirnov–Wolfenstein effect, where the electron density dominates. We find that the final neutrino content is composed by ∼55% (∼62%) of electronic neutrinos, i.e., {ν }e+{\\bar{ν }}e, for the normal (inverted) neutrino mass hierarchy. The results of this work are the first step toward the characterization of a novel source of astrophysical MeV neutrinos in addition to core-collapse SNe and, as such, deserve further attention.

Changes in tau phosphorylation in hibernating rodents.

PubMed

León-Espinosa, Gonzalo; García, Esther; García-Escudero, Vega; Hernández, Félix; Defelipe, Javier; Avila, Jesús

2013-07-01

Tau is a cytoskeletal protein present mainly in the neurons of vertebrates. By comparing the sequence of tau molecule among different vertebrates, it was found that the variability of the N-terminal sequence in tau protein is higher than that of the C-terminal region. The N-terminal region is involved mainly in the binding of tau to cellular membranes, whereas the C-terminal region of the tau molecule contains the microtubule-binding sites. We have compared the sequence of Syrian hamster tau with the sequences of other hibernating and nonhibernating rodents and investigated how differences in the N-terminal region of tau could affect the phosphorylation level and tau binding to cell membranes. We also describe a change, in tau phosphorylation, on a casein kinase 1 (ck1)-dependent site that is found only in hibernating rodents. This ck1 site seems to play an important role in the regulation of tau binding to membranes. Copyright © 2013 Wiley Periodicals, Inc.

An Experimentalist's Overview of Solar Neutrinos

NASA Astrophysics Data System (ADS)

Oser, Scott M.

2012-02-01

Four decades of solar neutrino research have demonstrated that solar models do a remarkable job of predicting the neutrino fluxes from the Sun, to the extent that solar neutrinos can now serve as a calibrated neutrino source for experiments to understand neutrino oscillations and mixing. In this review article I will highlight the most significant experimental results, with emphasis on the latest model-independent measurements from the Sudbury Neutrino Observatory. The solar neutrino fluxes are seen to be generally well-determined experimentally, with no indications of time variability, while future experiments will elucidate the lower energy part of the neutrino spectrum, especially pep and CNO neutrinos.

Search for sterile neutrino oscillations in muon neutrino disappearance at MINOS/MINOS+

NASA Astrophysics Data System (ADS)

Todd, Jacob; Minos+ Collaboration

2017-01-01

A wide variety of neutrino oscillation phenomena are well-described by the standard three-flavour neutrino model, but some anomalies exist. The LSND and MiniBooNE experiments have measured electron antineutrino appearance in excess of standard oscillation predictions, which points to the possibility of a sterile neutrino with higher mass than the presently known states. MINOS, a two-detector, long-baseline neutrino oscillation experiment, was optimized for the measurement of muon neutrino disappearance in the NuMI neutrino beam. A sterile neutrino responsible for the LSND and MiniBooNE excesses would cause distortions in the charged current and neutral current MINOS spectra, which permits the search for sterile neutrinos at MINOS. In close collaboration with the Daya Bay reactor neutrino experiment, MINOS has placed strong constraints on the sterile neutrino parameter space for a model with one additional sterile neutrino. Further, the extension of data collection with MINOS+, which samples the NuMI beam in a medium energy configuration, markedly increases the sensitivity of the combined MINOS and MINOS+ sample to a 3+1-flavour sterile neutrino model.

Overview of the Neutrinos from Stored Muons Facility - nuSTORM

DOE PAGES

Adey, D.; Appleby, R. B.; Bayes, R.; ...

2017-07-19

Neutrino beams produced from the decay of muons in a racetrack-like decay ring (the so called Neutrino Factory) provide a powerful way to study neutrino oscillation physics and, in addition, provide unique beams for neutrino interaction studies. The Neutrinos from STORed Muons (nuSTORM) facility uses a neutrino factory-like design. Due to the particular nature of nuSTORM, it can also provide an intense, very pure, muon neutrino beam from pion decay. This so-called 'Neo-conventional' muon-neutrino beam from nuSTORM makes nuSTORM a hybrid neutrino factory. Here in this paper we describe the facility and give a detailed description of the neutrino beamsmore » that are available and the precision to which they can be characterized. We then show its potential for a neutrino interaction physics program and present sensitivity plots that indicate how well the facility can perform for short-baseline oscillation searches. Lastly, we comment on the performance potential of a 'Neo-conventional' muon neutrino beam optimized for long-baseline neutrino-oscillation physics.« less

Neutrino masses, neutrino oscillations, and cosmological implications

NASA Technical Reports Server (NTRS)

Stecker, F. W.

1982-01-01

Theoretical concepts and motivations for considering neutrinos having finite masses are discussed and the experimental situation on searches for neutrino masses and oscillations is summarized. The solar neutrino problem, reactor, deep mine and accelerator data, tri decay experiments and double beta-decay data are considered and cosmological implications and astrophysical data relating to neutrino masses are reviewed. The neutrino oscillation solution to the solar neutrino problem, the missing mass problem in galaxy halos and galaxy cluster galaxy formation and clustering, and radiative neutrino decay and the cosmic ultraviolet background radiation are examined.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adey, D.; Appleby, R. B.; Bayes, R.

Neutrino beams produced from the decay of muons in a racetrack-like decay ring (the so called Neutrino Factory) provide a powerful way to study neutrino oscillation physics and, in addition, provide unique beams for neutrino interaction studies. The Neutrinos from STORed Muons (nuSTORM) facility uses a neutrino factory-like design. Due to the particular nature of nuSTORM, it can also provide an intense, very pure, muon neutrino beam from pion decay. This so-called 'Neo-conventional' muon-neutrino beam from nuSTORM makes nuSTORM a hybrid neutrino factory. Here in this paper we describe the facility and give a detailed description of the neutrino beamsmore » that are available and the precision to which they can be characterized. We then show its potential for a neutrino interaction physics program and present sensitivity plots that indicate how well the facility can perform for short-baseline oscillation searches. Lastly, we comment on the performance potential of a 'Neo-conventional' muon neutrino beam optimized for long-baseline neutrino-oscillation physics.« less

Specific serum antibody binding to phosphorylated and non-phosphorylated tau in non-cognitively impaired, mildly cognitively impaired, and Alzheimer's disease subjects: an exploratory study.

PubMed

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

2017-01-01

Tau vaccination and administration of anti-tau antibodies can prevent pathology and cognitive impairment in transgenic mouse models of tauopathy, suggesting that therapies which increase anti-tau antibodies might slow the development and/or progression of Alzheimer's disease (AD). The extent to which individuals with no cognitive impairment (NCI) possess serum anti-tau antibodies, and whether their concentrations of these antibodies differ from anti-tau antibody levels in persons with mild cognitive impairment (MCI) or AD, are unclear. Previous studies measuring these antibodies did not account for antibody polyvalent binding, which can be extensive, nor that antibody binding to phosphorylated tau peptides could be due to binding to non-phosphorylated epitopes on those peptides. An ELISA controlling for these factors was used to measure the specific binding of serum IgG and IgM to phosphorylated ("pTau;" phosphorylated at Serine-199 and Serine-202) and non-phosphorylated ("non-pTau") tau 196-207 in subjects with NCI, MCI, or AD ( n  = 10/group). Between-group differences in these antibody levels were evaluated for statistical significance, and correlations were examined in pooled data from all subjects between these antibody levels and subject age, global cognitive functioning, and NFT counts. Specific IgG binding to pTau and non-pTau was detected in all subjects except for one NCI control. Specific IgM binding was detected to pTau in all subjects except for two AD patients, and to non-pTau in all subjects. Mean pTau IgG was increased in MCI subjects by 53% and 70% vs. AD and NCI subjects respectively (both p  < 0.05), while no significant differences were found between groups for non-pTau IgG ( p  = 0.052), pTau IgM, or non-pTau IgM. Non-pTau IgG was negatively associated with global cognition (Spearman rho = -0.50). Specific binding of serum IgG and IgM to phosphorylated and non-phosphorylated tau may be present in older persons regardless of their cognitive status. Serum IgG to phosphorylated tau may be increased in individuals with MCI, but this unexpected finding requires confirmation. The approach used in this study to measure specific serum antibodies to phosphorylated tau should be useful for measuring antibodies to other post-translationally-modified proteins that are of relevance to neurodegenerative disorders.

Antisense reduction of tau in adult mice protects against seizures.

PubMed

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; Miller, Timothy M

2013-07-31

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.

Neuronal uptake and propagation of a rare phosphorylated high-molecular-weight tau derived from Alzheimer's disease brain

PubMed Central

Takeda, Shuko; Wegmann, Susanne; Cho, Hansang; DeVos, Sarah L.; Commins, Caitlin; Roe, Allyson D.; Nicholls, Samantha B.; Carlson, George A.; Pitstick, Rose; Nobuhara, Chloe K.; Costantino, Isabel; Frosch, Matthew P.; Müller, Daniel J.; Irimia, Daniel; Hyman, Bradley T.

2015-01-01

Tau pathology is known to spread in a hierarchical pattern in Alzheimer's disease (AD) brain during disease progression, likely by trans-synaptic tau transfer between neurons. However, the tau species involved in inter-neuron propagation remains unclear. To identify tau species responsible for propagation, we examined uptake and propagation properties of different tau species derived from postmortem cortical extracts and brain interstitial fluid of tau-transgenic mice, as well as human AD cortices. Here we show that PBS-soluble phosphorylated high-molecular-weight (HMW) tau, though very low in abundance, is taken up, axonally transported, and passed on to synaptically connected neurons. Our findings suggest that a rare species of soluble phosphorylated HMW tau is the endogenous form of tau involved in propagation and could be a target for therapeutic intervention and biomarker development. PMID:26458742

Neutrino mixing and big bang nucleosynthesis

NASA Astrophysics Data System (ADS)

Bell, Nicole

2003-04-01

We analyse active-active neutrino mixing in the early universe and show that transformation of neutrino-antineutrino asymmetries between flavours is unavoidable when neutrino mixing angles are large. This process is a standard Mikheyev-Smirnov-Wolfenstein flavour transformation, modified by the synchronisation of momentum states which results from neutrino-neutrino forward scattering. The new constraints placed on neutrino asymmetries eliminate the possibility of degenerate big bang nucleosynthesis.Implications of active-sterile neutrino mixing will also be reviewed.

The Intermediate Neutrino Program

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adams, C.; Alonso, J. R.; Ankowski, A. M.

2017-04-03

The US neutrino community gathered at the Workshop on the Intermediate Neutrino Program (WINP) at Brookhaven National Laboratory February 4-6, 2015 to explore opportunities in neutrino physics over the next five to ten years. Scientists from particle, astroparticle and nuclear physics participated in the workshop. The workshop examined promising opportunities for neutrino physics in the intermediate term, including possible new small to mid-scale experiments, US contributions to large experiments, upgrades to existing experiments, R&D plans and theory. The workshop was organized into two sets of parallel working group sessions, divided by physics topics and technology. Physics working groups covered topicsmore » on Sterile Neutrinos, Neutrino Mixing, Neutrino Interactions, Neutrino Properties and Astrophysical Neutrinos. Technology sessions were organized into Theory, Short-Baseline Accelerator Neutrinos, Reactor Neutrinos, Detector R&D and Source, Cyclotron and Meson Decay at Rest sessions.This report summarizes discussion and conclusions from the workshop.« less

The Neutrino: A Better Understanding Through Astrophysics: Final Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kneller, James P.

The final report for the award "The Neutrino: A Better Understanding Through Astrophysics" is given. The goals of the work were the following: to construct new theoretical approaches to the problem of neutrino propagation in media including where neutrino-neutrino interactions are important; to pioneer the use of new approaches, including super-scattering operators, for the evolution of neutrino thermal and statistical ensembles; to implement these new approaches in computer codes to study neutrino evolution in supernovae and other hot, dense environments; to increase the realism of simulated signals of a Galactic supernovae neutrino burst in current and future neutrino detectors; tomore » study the simulated signals to determine the ability to extract information on the missing neutrino mixing parameters and the dynamics of the supernova explosion; and to study sterile neutrinos and non-standard interactions of neutrinos in supernovae and their effect upon the signal. Accomplishments made in these areas are described.« less

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Askew, Andrew; Jaiswal, Prerit; Okui, Takemichi

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 \

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

DOE PAGES

Askew, Andrew; Jaiswal, Prerit; Okui, Takemichi; ...

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 \

Retarded axonal transport of R406W mutant tau in transgenic mice with a neurodegenerative tauopathy.

PubMed

Zhang, Bin; Higuchi, Makoto; Yoshiyama, Yasumasa; Ishihara, Takeshi; Forman, Mark S; Martinez, Dan; Joyce, Sonali; Trojanowski, John Q; Lee, Virginia M-Y

2004-05-12

Intracellular accumulations of filamentous tau inclusions are neuropathological hallmarks of neurodegenerative diseases known as tauopathies. The discovery of multiple pathogenic tau gene mutations in many kindreds with familial frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) unequivocally confirmed the central role of tau abnormalities in the etiology of neurodegenerative disorders. To examine the effects of tau gene mutations and the role of tau abnormalities in neurodegenerative tauopathies, transgenic (Tg) mice were engineered to express the longest human tau isoform (T40) with or without the R406W mutation (RW and hWT Tg mice, respectively) that is pathogenic for FTDP-17 in several kindreds. RW but not hWT tau Tg mice developed an age-dependent accumulation of insoluble filamentous tau aggregates in neuronal perikarya of the cerebral cortex, hippocampus, cerebellum, and spinal cord. Significantly, CNS axons in RW mice contained reduced levels of tau when compared with hWT mice, and this was linked to retarded axonal transport and increased accumulation of an insoluble pool of RW but not hWT tau. Furthermore, RW but not hWT mice demonstrated neurodegeneration and a reduced lifespan. These data indicate that the R406W mutation causes reduced binding of this mutant tau to microtubules, resulting in slower axonal transport. This altered tau function caused by the RW mutation leads to increased accumulation and reduced solubility of RW tau in an age-dependent manner, culminating in the formation of filamentous intraneuronal tau aggregates similar to that observed in tauopathy patients.

An Unbiased Approach to Identifying Tau Kinases That Phosphorylate Tau at Sites Associated with Alzheimer Disease

PubMed Central

Cavallini, Annalisa; Brewerton, Suzanne; Bell, Amanda; Sargent, Samantha; Glover, Sarah; Hardy, Clare; Moore, Roger; Calley, John; Ramachandran, Devaki; Poidinger, Michael; Karran, Eric; Davies, Peter; Hutton, Michael; Szekeres, Philip; Bose, Suchira

2013-01-01

Neurofibrillary tangles, one of the hallmarks of Alzheimer disease (AD), are composed of paired helical filaments of abnormally hyperphosphorylated tau. The accumulation of these proteinaceous aggregates in AD correlates with synaptic loss and severity of dementia. Identifying the kinases involved in the pathological phosphorylation of tau may identify novel targets for AD. We used an unbiased approach to study the effect of 352 human kinases on their ability to phosphorylate tau at epitopes associated with AD. The kinases were overexpressed together with the longest form of human tau in human neuroblastoma cells. Levels of total and phosphorylated tau (epitopes Ser(P)-202, Thr(P)-231, Ser(P)-235, and Ser(P)-396/404) were measured in cell lysates using AlphaScreen assays. GSK3α, GSK3β, and MAPK13 were found to be the most active tau kinases, phosphorylating tau at all four epitopes. We further dissected the effects of GSK3α and GSK3β using pharmacological and genetic tools in hTau primary cortical neurons. Pathway analysis of the kinases identified in the screen suggested mechanisms for regulation of total tau levels and tau phosphorylation; for example, kinases that affect total tau levels do so by inhibition or activation of translation. A network fishing approach with the kinase hits identified other key molecules putatively involved in tau phosphorylation pathways, including the G-protein signaling through the Ras family of GTPases (MAPK family) pathway. The findings identify novel tau kinases and novel pathways that may be relevant for AD and other tauopathies. PMID:23798682

Tau Positive Neurons Show Marked Mitochondrial Loss and Nuclear Degradation in Alzheimer's Disease.

PubMed

Wee, Melissa; Chegini, Fariba; Power, John H T; Majd, Shohreh

2018-06-12

Alzheimer's disease (AD) pathology consists of intraneuronal neurofibrillary tangles, made of hyperphosphorylated tau and extracellular accumulation of beta amyloid (Aβ) in Aβ plaques. There is an extensive debate as to which pathology initiates and responsible for cellular loss in AD. Using confocal and light microscopy, post mortem brains from control and AD cases, an antibody to SOD2 as a marker for mitochondria and an antibody to all forms of tau, we analyzed mitochondrial density in tau positive neurons along with nuclear degradation by calculating the raw integrative density. Our findings showed an extensive staining of aggregated tau in cell bodies, dystrophic neurites and neurofilaments in AD with minimal staining in control tissue, along with a marked decrease in mitochondria in tau positive (tau+) neurons. The control or tau negative (tau-) neurons in AD contained an even distribution of mitochondria, which was greatly diminished in tau+ neurons by 40%. There were no significant differences between control and tau- neurons in AD. Tau+ neurons showed marked nuclear degradation which appeared to progress with the extent of tau aggregation. The aggregated tau infiltrated and appeared to break the nuclear envelope with progressively more DNA exiting the nucleus and associating with accumulating of intracellular tau. We report mitochondrial decrease is likely due to a decrease in protein synthesis rather than a redistribution of mitochondria because of decreased axonal transport. We suggest that the decrease in mitochondria and nuclear degradation are key mechanisms for the neuronal loss seen in AD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Calculation of Left Ventricular Diastolic Time Constant (TAU) in Dogs with Mitral Regurgitation Using Continuous-Wave Doppler.

PubMed

Wen, Chaoyang; Sun, Jing; Fan, Chunzhi; Dou, Jianping

2018-05-04

The left ventricular diastolic time constant (Tau) cannot be practically measured non-invasively. Thus, the aim of this study was to investigate a new method for the evaluation of Tau using continuous-wave (CW) Doppler in dogs with mitral regurgitation. Guided by ultrasound, we created 12 beagle models of mitral regurgitation and acute ischemic left ventricular diastolic dysfunction. Raw audio signals of the CW Doppler spectra were collected, and new mitral regurgitation Doppler spectra were observed after computer re-processing. The new Doppler spectra contour line was constructed using MATLAB (Version R2009), and two time intervals, t1-t2 and t1-t3, were measured on the descending branch of the mitral regurgitation Doppler spectrum and were substituted into Bai's equation group. The Doppler-derived Tau (Tau-d) was resolved and compared with the simultaneous catheter-derived Tau (Tau-c). No significant difference (p > 0.05) between Tau-d (49.33 ± 18.79 ms) and Tau-c (48.76 ± 17.60 ms) was found. A correlation analysis between Tau-d and Tau-c suggested a strong positive relationship (r = 0.85, p = 0.000). Bland-Altman plots of Tau-d and Tau-c revealed fair agreement. Compared with previous non-invasive approaches, this method is simpler and more accurate. There is a strong positive relationship and fair agreement between Tau-d and Tau-c. Copyright © 2018 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.

Experimental Neutrino Physics: Final Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lane, Charles E.; Maricic, Jelena

2012-09-05

Experimental studies of neutrino properties, with particular emphasis on neutrino oscillation, mass and mixing parameters. This research was pursued by means of underground detectors for reactor anti-neutrinos, measuring the flux and energy spectra of the neutrinos. More recent investigations have been aimed and developing detector technologies for a long-baseline neutrino experiment (LBNE) using a neutrino beam from Fermilab.

Biology, taxonomy, and IPM strategies of Bactrocera tau Walker and complex species (Diptera; Tephritidae) in Asia: a comprehensive review.

PubMed

Jaleel, Waqar; Lu, Lihua; He, Yurong

2018-06-02

Bactrocera flies are the serious pests of fruit, vegetables, and nuts over the world. Bactrocera tau Walker is an economically important pest of agricultural crops. In Asia, approximately 30-40% losses of agricultural products are caused by B. tau infestation every year. In Asia, the B. tau contains a complex of sibling species that called the tau complex. However, the basic studies of B. tau and complex species are very important for integrated management. A comprehensive review of the B. tau and complex species has not been provided elsewhere. So, considering the importance of B. tau and complex species, this study provides the published information on ecology, nomenclature, identification tools, geographical distribution, potential invasion, and IPM tactics of B. tau and complex species, which would be more informative for publication facilitating related to integrated pest management (IPM) strategies of B. tau and complex species. In IPM of B. tau and complex species, the phytochemical and biological controls have not been applied successfully in Asia; there is an urgent need to study and applications of these two mentioned control techniques against the B. tau and complex species in Asia.

Insulin deprivation induces PP2A inhibition and tau hyperphosphorylation in hTau mice, a model of Alzheimer’s disease-like tau pathology

PubMed Central

Gratuze, Maud; Julien, Jacinthe; Petry, Franck R.; Morin, Françoise; Planel, Emmanuel

2017-01-01

Abnormally hyperphosphorylated tau aggregated as intraneuronal neurofibrillary tangles is one of the two neuropathological hallmarks of Alzheimer’s disease (AD). The majority of AD cases are sporadic with numerous environmental, biological and genetic risks factors. Interestingly, insulin dysfunction and hyperglycaemia are both risk factors for sporadic AD. However, how hyperglycaemia and insulin dysfunction affect tau pathology, is not well understood. In this study, we examined the effects of insulin deficiency on tau pathology in transgenic hTau mice by injecting different doses of streptozotocin (STZ), a toxin that destroys insulin-producing cells in the pancreas. One high dose of STZ resulted in marked diabetes, and five low doses led to a milder diabetes. Both groups exhibited brain tau hyperphosphorylation but no increased aggregation. Tau hyperphosphorylation correlated with inhibition of Protein Phosphatase 2A (PP2A), the main tau phosphatase. Interestingly, insulin injection 30 minutes before sacrifice partially restored tau phosphorylation to control levels in both STZ-injected groups. Our results confirm a link between insulin homeostasis and tau phosphorylation, which could explain, at least in part, a higher incidence of AD in diabetic patients. PMID:28402338

Insulin deprivation induces PP2A inhibition and tau hyperphosphorylation in hTau mice, a model of Alzheimer's disease-like tau pathology.

PubMed

Gratuze, Maud; Julien, Jacinthe; Petry, Franck R; Morin, Françoise; Planel, Emmanuel

2017-04-12

Abnormally hyperphosphorylated tau aggregated as intraneuronal neurofibrillary tangles is one of the two neuropathological hallmarks of Alzheimer's disease (AD). The majority of AD cases are sporadic with numerous environmental, biological and genetic risks factors. Interestingly, insulin dysfunction and hyperglycaemia are both risk factors for sporadic AD. However, how hyperglycaemia and insulin dysfunction affect tau pathology, is not well understood. In this study, we examined the effects of insulin deficiency on tau pathology in transgenic hTau mice by injecting different doses of streptozotocin (STZ), a toxin that destroys insulin-producing cells in the pancreas. One high dose of STZ resulted in marked diabetes, and five low doses led to a milder diabetes. Both groups exhibited brain tau hyperphosphorylation but no increased aggregation. Tau hyperphosphorylation correlated with inhibition of Protein Phosphatase 2A (PP2A), the main tau phosphatase. Interestingly, insulin injection 30 minutes before sacrifice partially restored tau phosphorylation to control levels in both STZ-injected groups. Our results confirm a link between insulin homeostasis and tau phosphorylation, which could explain, at least in part, a higher incidence of AD in diabetic patients.

Measuring B{sup {+-}}{yields}{tau}{sup {+-}}{nu} and B{sub c}{sup {+-}}{yields}{tau}{sup {+-}}{nu} at the Z peak

DOE Office of Scientific and Technical Information (OSTI.GOV)

Akeroyd, A. G.; Chen, C.H.; National Center for Theoretical Sciences, Taiwan

2008-06-01

The measurement of B{sup {+-}}{yields}{tau}{sup {+-}}{nu}{sub {tau}} at the B factories provides important constraints on the parameter tan{beta}/m{sub H{sup {+-}}} in the context of models with two Higgs doublets. Limits on this decay from e{sup +}e{sup -} collisions at the Z peak were sensitive to the sum of B{sup {+-}}{yields}{tau}{sup {+-}}{nu}{sub {tau}} and B{sub c}{sup {+-}}{yields}{tau}{sup {+-}}{nu}{sub {tau}}. Because of the possibly sizeable contribution from B{sub c}{sup {+-}}{yields}{tau}{sup {+-}}{nu}{sub {tau}} we suggest that a signal for this combination might be observed if the CERN LEP L3 Collaboration used its total data of {approx}3.6x10{sup 6} hadronic decays of the Z boson.more » Moreover, we point out that a future linear collider operating at the Z peak (Giga Z option) could constrain tan{beta}/m{sub H{sup {+-}}} from the sum of these processes with a precision comparable to that anticipated at proposed high luminosity B factories from B{sup {+-}}{yields}{tau}{sup {+-}}{nu}{sub {tau}} alone.« less

Inhibition of glycogen synthase kinase-3beta downregulates total tau proteins in cultured neurons and its reversal by the blockade of protein phosphatase-2A.

PubMed

Martin, Ludovic; Magnaudeix, Amandine; Esclaire, Françoise; Yardin, Catherine; Terro, Faraj

2009-02-03

In tauopathies such as Alzheimer's disease (AD), the molecular mechanisms of tau protein aggregation into neurofibrillary tangles (NFTs) and their contribution to neurodegeneration remain not understood. It was recently demonstrated that tau, regardless of its aggregation, might represent a key mediator of neurodegeneration. Therefore, reduction of tau levels might represent a mechanism of neuroprotection. Glycogen synthase kinase-3beta (GSK3beta) and protein phosphatase-2A (PP2A) are key enzymes involved in the regulation of tau phosphorylation, and have been suggested to be involved in the abnormal tau phosphorylation and aggregation in AD. Connections between PP2A and GSK3beta signaling have been reported. We have previously demonstrated that exposure of cultured cortical neurons to lithium decreased tau protein expression and provided neuroprotection against Abeta. Since lithium is not a specific inhibitor of GSK3beta (ID50=2.0 mM), whether or not the lithium-induced tau decrease involves GSK3beta remained to be determined. For that purpose, cultured cortical neurons were exposed to 6-bromo-indirubin-3'-oxime (6-BIO), a more selective and potent GSK3beta inhibitor (ID50=1.5 microM) or to lithium. Analysis of tau levels and phosphorylation by western-blot assays showed that lithium and 6-BIO dose-dependently decreased both tau protein levels and tau phosphorylation. Conversely, inhibition of cyclin-dependent kinase-5 (CDK5) by roscovitine decreased phosphorylated tau but failed to alter tau protein levels. These data indicate that GSK3beta might be selectively involved in the regulation of tau protein levels. Moreover, inhibition of PP2A by okadaic acid, but not that of PP2B (protein phosphatase-2B)/calcineurin by FK506, dose-dependently reversed lithium-induced tau decrease. These data indicate that GSK3beta regulates both tau phosphorylation and total tau levels through PP2A.

Detection of extended galactic sources with an underwater neutrino telescope

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leisos, A.; Tsirigotis, A. G.; Tzamarias, S. E.

2014-11-18

In this study we investigate the discovery capability of a Very Large Volume Neutrino Telescope to Galactic extended sources. We focus on the brightest HESS gamma rays sources which are considered also as very high energy neutrino emitters. We use the unbinned method taking into account both the spatial and the energy distribution of high energy neutrinos and we investigate parts of the Galactic plane where nearby potential neutrino emitters form neutrino source clusters. Neutrino source clusters as well as isolated neutrino sources are combined to estimate the observation period for 5 sigma discovery of neutrino signals from these objects.

Neutrino oscillation studies with reactors

PubMed Central

Vogel, P.; Wen, L.J.; Zhang, C.

2015-01-01

Nuclear reactors are one of the most intense, pure, controllable, cost-effective and well-understood sources of neutrinos. Reactors have played a major role in the study of neutrino oscillations, a phenomenon that indicates that neutrinos have mass and that neutrino flavours are quantum mechanical mixtures. Over the past several decades, reactors were used in the discovery of neutrinos, were crucial in solving the solar neutrino puzzle, and allowed the determination of the smallest mixing angle θ13. In the near future, reactors will help to determine the neutrino mass hierarchy and to solve the puzzling issue of sterile neutrinos. PMID:25913819

Astrophysical and cosmological constraints to neutrino properties

NASA Technical Reports Server (NTRS)

Kolb, Edward W.; Schramm, David N.; Turner, Michael S.

1989-01-01

The astrophysical and cosmological constraints on neutrino properties (masses, lifetimes, numbers of flavors, etc.) are reviewed. The freeze out of neutrinos in the early Universe are discussed and then the cosmological limits on masses for stable neutrinos are derived. The freeze out argument coupled with observational limits is then used to constrain decaying neutrinos as well. The limits to neutrino properties which follow from SN1987A are then reviewed. The constraint from the big bang nucleosynthesis on the number of neutrino flavors is also considered. Astrophysical constraints on neutrino-mixing as well as future observations of relevance to neutrino physics are briefly discussed.

Solar neutrino detectors as sterile neutrino hunters

NASA Astrophysics Data System (ADS)

Pallavicini, Marco; Borexino-SOX Collaboration; Agostini, M.; Altenmüller, K.; Appel, S.; Atroshchenko, V.; Bellini, G.; Benziger, J.; Berton, N.; Bick, D.; Bonfini, G.; Bravo, D.; Caccianiga, B.; Calaprice, F.; Caminata, A.; Carlini, M.; Cavalcante, P.; Chepurnov, A.; Choi, K.; Cloué, O.; Cribier, M.; D'Angelo, D.; Davini, S.; Derbin, A.; Di Noto, L.; Drachnev, I.; Durero, M.; Etenko, A.; Farinon, S.; Fischer, V.; Fomenko, K.; Franco, D.; Gabriele, F.; Gaffiot, J.; Galbiati, C.; Gschwender, M.; Ghiano, C.; Giammarchi, M.; Goeger-Neff, M.; Goretti, A.; Gromov, M.; Hagner, C.; Houdy, Th.; Hungerford, E.; Ianni, Aldo; Ianni, Andrea; Jany, A.; Jedrzejczak, K.; Jeschke, D.; Jonquères, N.; Kobychev, V.; Korablev, D.; Korga, G.; Kornoukhov, V.; Kryn, D.; Lachenmaier, T.; Lasserre, T.; Laubenstein, M.; Lehnert, B.; Link, J.; Litvinovich, E.; Lombardi, F.; Lombardi, P.; Ludhova, L.; Lukyanchenko, G.; Machulin, I.; Manecki, S.; Maneschg, W.; Marcocci, S.; Maricic, J.; Mention, G.; Meroni, E.; Meyer, M.; Miramonti, L.; Misiaszek, M.; Montuschi, M.; Mosteiro, P.; Muratova, V.; Musenich, R.; Neumair, B.; Oberauer, L.; Ortica, F.; Papp, L.; Pocar, A.; Ranucci, G.; Razeto, A.; Re, A.; Reinert, Y.; Romani, A.; Roncin, R.; Rossi, N.; Schönert, S.; Scola, L.; Semenov, D.; Skorokhvatov, M.; Smirnov, O.; Sotnikov, A.; Suvorov, Y.; Tartaglia, R.; Testera, G.; Thurn, J.; Toropova, M.; Unzhakov, E.; Veyssière, C.; Vishneva, A.; Vivier, M.; Vogelaar, R. B.; von Feilitzsch, F.; Wang, H.; Weinz, S.; Winter, J.; Wojcik, M.; Wurm, M.; Yokley, Z.; Zaimidoroga, O.; Zavatarelli, S.; Zuber, K.; Zuzel, G.

2017-09-01

The large size and the very low radioactive background of solar neutrino detectors such as Borexino at the Gran Sasso Laboratory in Italy offer a unique opportunity to probe the existence of neutrino oscillations into new sterile components by means of carefully designed and well calibrated anti-neutrino and neutrino artificial sources. In this paper we briefly summarise the key elements of the SOX experiment, a program for the search of sterile neutrinos (and other short distance effects) by means of a 144Ce-144Pr anti-neutrino source and, possibly in the medium term future, with a 51Cr neutrino source.

Neutrino masses in the minimal gauged (B -L ) supersymmetry

NASA Astrophysics Data System (ADS)

Yan, Yu-Li; Feng, Tai-Fu; Yang, Jin-Lei; Zhang, Hai-Bin; Zhao, Shu-Min; Zhu, Rong-Fei

2018-03-01

We present the radiative corrections to neutrino masses in a minimal supersymmetric extension of the standard model with local U (1 )B -L symmetry. At tree level, three tiny active neutrinos and two nearly massless sterile neutrinos can be obtained through the seesaw mechanism. Considering the one-loop corrections to the neutrino masses, the numerical results indicate that two sterile neutrinos obtain KeV masses and the small active-sterile neutrino mixing angles. The lighter sterile neutrino is a very interesting dark matter candidate in cosmology. Meanwhile, the active neutrinos mixing angles and mass squared differences agree with present experimental data.

Neutrino oscillation studies with reactors

DOE PAGES

Vogel, P.; Wen, L.J.; Zhang, C.

2015-04-27

Nuclear reactors are one of the most intense, pure, controllable, cost-effective and well-understood sources of neutrinos. Reactors have played a major role in the study of neutrino oscillations, a phenomenon that indicates that neutrinos have mass and that neutrino flavours are quantum mechanical mixtures. Over the past several decades, reactors were used in the discovery of neutrinos, were crucial in solving the solar neutrino puzzle, and allowed the determination of the smallest mixing angle θ 13. In the near future, reactors will help to determine the neutrino mass hierarchy and to solve the puzzling issue of sterile neutrinos.

Neutrino oscillation studies with reactors.

PubMed

Vogel, P; Wen, L J; Zhang, C

2015-04-27

Nuclear reactors are one of the most intense, pure, controllable, cost-effective and well-understood sources of neutrinos. Reactors have played a major role in the study of neutrino oscillations, a phenomenon that indicates that neutrinos have mass and that neutrino flavours are quantum mechanical mixtures. Over the past several decades, reactors were used in the discovery of neutrinos, were crucial in solving the solar neutrino puzzle, and allowed the determination of the smallest mixing angle θ13. In the near future, reactors will help to determine the neutrino mass hierarchy and to solve the puzzling issue of sterile neutrinos.

BAG3 facilitates the clearance of endogenous tau in primary neurons.

PubMed

Lei, Zhinian; Brizzee, Corey; Johnson, Gail V W

2015-01-01

Tau is a microtubule associated protein that is found primarily in neurons, and in pathologic conditions, such as Alzheimer's disease (AD) it accumulates and contributes to the disease process. Because tau plays a fundamental role in the pathogenesis of AD and other tauopathies, and in AD mouse models reducing tau levels improves outcomes, approaches that facilitate tau clearance are being considered as therapeutic strategies. However, fundamental to the development of such interventions is a clearer understanding of the mechanisms that regulate tau clearance. Here, we report a novel mechanism of tau degradation mediated by the co-chaperone BAG3. BAG3 has been shown to be an essential component of a complex that targets substrates to the autophagy pathway for degradation. In rat primary neurons, activation of autophagy by inhibition of proteasome activity or treatment with trehalose resulted in significant decreases in tau and phospho-tau levels. These treatments also induced an upregulation of BAG3. Proteasome inhibition activated JNK, which was responsible for the upregulation of BAG3 and increased tau clearance. Inhibiting JNK or knocking down BAG3 blocked the proteasome inhibition-induced decreases in tau. Further, BAG3 overexpression alone resulted in significant decreases in tau and phospho-tau levels in neurons. These results indicate that BAG3 plays a critical role in regulating the levels of tau in neurons, and interventions that increase BAG3 levels could provide a therapeutic approach in the treatment of AD. Copyright © 2015 Elsevier Inc. All rights reserved.

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

Hsp90 activator Aha1 drives production of pathological tau aggregates

PubMed Central

Shelton, Lindsey B.; Baker, Jeremy D.; Zheng, Dali; Sullivan, Leia E.; Solanki, Parth K.; Webster, Jack M.; Sun, Zheying; Sabbagh, Jonathan J.; Nordhues, Bryce A.; Koren, John; Ghosh, Suman; Blagg, Brian S. J.; Dickey, Chad A.

2017-01-01

The microtubule-associated protein tau (MAPT, tau) forms neurotoxic aggregates that promote cognitive deficits in tauopathies, the most common of which is Alzheimer’s disease (AD). The 90-kDa heat shock protein (Hsp90) chaperone system affects the accumulation of these toxic tau species, which can be modulated with Hsp90 inhibitors. However, many Hsp90 inhibitors are not blood–brain barrier-permeable, and several present associated toxicities. Here, we find that the cochaperone, activator of Hsp90 ATPase homolog 1 (Aha1), dramatically increased the production of aggregated tau. Treatment with an Aha1 inhibitor, KU-177, dramatically reduced the accumulation of insoluble tau. Aha1 colocalized with tau pathology in human brain tissue, and this association positively correlated with AD progression. Aha1 overexpression in the rTg4510 tau transgenic mouse model promoted insoluble and oligomeric tau accumulation leading to a physiological deficit in cognitive function. Overall, these data demonstrate that Aha1 contributes to tau fibril formation and neurotoxicity through Hsp90. This suggests that therapeutics targeting Aha1 may reduce toxic tau oligomers and slow or prevent neurodegenerative disease progression. PMID:28827321

Search for Sterile Neutrinos Using the MiniBooNE Beam

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sorel, Michel

2005-01-01

The possible existence of light sterile neutrinos in Nature is motivated, and the prospects to extend sterile neutrino searches beyond current limits is substantiated, using the MiniBooNE neutrino beam and detector at Fermilab. We report on the neutrino flux predictions for the MiniBooNE experiment, on the characterization of the charged-current, quasi-elastic interactions of muon neutrinos ({nu}{sub {mu}}n {yields} {mu}{sup -}p) observed, and on the experiment's sensitivity to sterile neutrinos via muon neutrino disappearance.

Structural elucidation of the interaction between neurodegenerative disease-related tau protein with model lipid membranes

NASA Astrophysics Data System (ADS)

Jones, Emmalee M.

A protein's sequence of amino acids determines how it folds. That folded structure is linked to protein function, and misfolding to dysfunction. Protein misfolding and aggregation into beta-sheet rich fibrillar aggregates is connected with over 20 neurodegenerative diseases, including Alzheimer's disease (AD). AD is characterized in part by misfolding, aggregation and deposition of the microtubule associated tau protein into neurofibrillary tangles (NFTs). However, two questions remain: What is tau's fibrillization mechanism, and what is tau's cytotoxicity mechanism? Tau is prone to heterogeneous interactions, including with lipid membranes. Lipids have been found in NFTs, anionic lipid vesicles induced aggregation of the microtubule binding domain of tau, and other protein aggregates induced ion permeability in cells. This evidence prompted our investigation of tau's interaction with model lipid membranes to elucidate the structural perturbations those interactions induced in tau protein and in the membrane. We show that although tau is highly charged and soluble, it is highly surface active and preferentially interacts with anionic membranes. To resolve molecular-scale structural details of tau and model membranes, we utilized X-ray and neutron scattering techniques. X-ray reflectivity indicated tau aggregated at air/water and anionic lipid membrane interfaces and penetrated into membranes. More significantly, membrane interfaces induced tau protein to partially adopt a more compact conformation with density similar to folded protein and ordered structure characteristic of beta-sheet formation. This suggests possible membrane-based mechanisms of tau aggregation. Membrane morphological changes were seen using fluorescence microscopy, and X-ray scattering techniques showed tau completely disrupts anionic membranes, suggesting an aggregate-based cytotoxicity mechanism. Further investigation of protein constructs and a "hyperphosphorylation" disease mimic helped clarify the role of the microtubule binding domain in anionic lipid affinity and demonstrated even "hyperphosphorylation" did not prevent interaction with anionic membranes. Additional studies investigated more complex membrane models to increase physiological relevance. These insights revealed structural changes in tau protein and lipid membranes after interaction. We observed tau's affinity for interfaces, and aggregation and compaction once tau partitions to interfaces. We observed the beginnings of beta-sheet formation in tau at anionic lipid membranes. We also examined disruption to the membrane on a molecular scale.

Associations between [18F]AV1451 tau PET and CSF measures of tau pathology in a clinical sample.

PubMed

La Joie, Renaud; Bejanin, Alexandre; Fagan, Anne M; Ayakta, Nagehan; Baker, Suzanne L; Bourakova, Viktoriya; Boxer, Adam L; Cha, Jungho; Karydas, Anna; Jerome, Gina; Maass, Anne; Mensing, Ashley; Miller, Zachary A; O'Neil, James P; Pham, Julie; Rosen, Howard J; Tsai, Richard; Visani, Adrienne V; Miller, Bruce L; Jagust, William J; Rabinovici, Gil D

2018-01-23

To assess the relationships between fluid and imaging biomarkers of tau pathology and compare their diagnostic utility in a clinically heterogeneous sample. Fifty-three patients (28 with clinical Alzheimer disease [AD] and 25 with non-AD clinical neurodegenerative diagnoses) underwent β-amyloid (Aβ) and tau ([ 18 F]AV1451) PET and lumbar puncture. CSF biomarkers (Aβ 42 , total tau [t-tau], and phosphorylated tau [p-tau]) were measured by multianalyte immunoassay (AlzBio3). Receiver operator characteristic analyses were performed to compare discrimination of Aβ-positive AD from non-AD conditions across biomarkers. Correlations between CSF biomarkers and PET standardized uptake value ratios (SUVR) were assessed using skipped Pearson correlation coefficients. Voxelwise analyses were run to assess regional CSF-PET associations. [ 18 F]AV1451-PET cortical SUVR and p-tau showed excellent discrimination between Aβ-positive AD and non-AD conditions (area under the curve 0.92-0.94; ≤0.83 for other CSF measures), and reached 83% classification agreement. In the full sample, cortical [ 18 F]AV1451 was associated with all CSF biomarkers, most strongly with p-tau ( r = 0.75 vs 0.57 for t-tau and -0.49 for Aβ 42 ). When restricted to Aβ-positive patients with AD, [ 18 F]AV1451 SUVR correlated modestly with p-tau and t-tau (both r = 0.46) but not Aβ 42 ( r = 0.02). On voxelwise analysis, [ 18 F]AV1451 correlated with CSF p-tau in temporoparietal cortices and with t-tau in medial prefrontal regions. Within AD, Mini-Mental State Examination scores were associated with [ 18 F]AV1451-PET, but not CSF biomarkers. [ 18 F]AV1451-PET and CSF p-tau had comparable value for differential diagnosis. Correlations were robust in a heterogeneous clinical group but attenuated (although significant) in AD, suggesting that fluid and imaging biomarkers capture different aspects of tau pathology. This study provides Class III evidence that, in a clinical sample of patients with a variety of suspected neurodegenerative diseases, both CSF p-tau and [ 18 F]AV1451 distinguish AD from non-AD conditions. Copyright © 2017 American Academy of Neurology.

Collective neutrino oscillations and neutrino wave packets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Akhmedov, Evgeny; Lindner, Manfred; Kopp, Joachim, E-mail: akhmedov@mpi-hd.mpg.de, E-mail: jkopp@uni-mainz.de, E-mail: lindner@mpi-hd.mpg.de

Effects of decoherence by wave packet separation on collective neutrino oscillations in dense neutrino gases are considered. We estimate the length of the wave packets of neutrinos produced in core collapse supernovae and the expected neutrino coherence length, and then proceed to consider the decoherence effects within the density matrix formalism of neutrino flavour transitions. First, we demonstrate that for neutrino oscillations in vacuum the decoherence effects are described by a damping term in the equation of motion of the density matrix of a neutrino as a whole (as contrasted to that of the fixed-momentum components of the neutrino densitymore » matrix). Next, we consider neutrino oscillations in ordinary matter and dense neutrino backgrounds, both in the adiabatic and non-adiabatic regimes. In the latter case we study two specific models of adiabaticity violation—one with short-term and another with extended non-adiabaticity. It is demonstrated that, while in the adiabatic case a damping term is present in the equation of motion of the neutrino density matrix (just like in the vacuum oscillation case), no such term in general appears in the non-adiabatic regime.« less

Neutrino Detectors

NASA Astrophysics Data System (ADS)

von Feilitzsch, Franz; Lanfranchi, Jean-Côme; Wurm, Michael

The neutrino was postulated by Wolfgang Pauli in the early 1930s, but could only be detected for the first time in the 1950s. Ever since scientists all around the world have worked on the detection and understanding of this particle which so scarcely interacts with matter. Depending on the origin and nature of the neutrino, various types of experiments have been developed and operated. In this entry, we will review neutrino detectors in terms of neutrino energy and associated detection technique as well as the scientific outcome of some selected examples. After a brief historical introduction, the detection of low-energy neutrinos originating from nuclear reactors or from the Earth is used to illustrate the principles and difficulties which are encountered in detecting neutrinos. In the context of solar neutrino spectroscopy, where the neutrino is used as a probe for astrophysics, three different types of neutrino detectors are presented - water Čerenkov, radiochemical, and liquid-scintillator detectors. Moving to higher neutrino energies, we discuss neutrinos produced by astrophysical sources and from accelerators. The entry concludes with an overview of a selection of future neutrino experiments and their scientific goals.

Status of the nuSTORM Facility and a Possible Extension for Long-Baseline $$\

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bross, Alan D.; Liu, Ao; Lagrange, Jean-Baptiste

2015-11-03

Neutrino beams produced from the decay of muons in a racetrack-like decay ring (the so called Neutrino Factory) provide a powerful way to study neutrino oscillation physics and, in addition, provide unique beams for neutrino interaction studies. The Neutrinos from STORed Muons (nuSTORM) facility uses a neutrino factory-like design. Due to the particular nature of nuSTORM, it can also provide an intense, very pure, muon neutrino beam from pion decay. This so-called “Neo-conventional" muon neutrino beam from nuSTORM makes nuSTORM a hybrid neutrino factory. In this paper we describe the facility and give a detailed description of the neutrino beammore » fluxes that are available and the precision to which these fluxes can be determined. We then present sensitivity plots that indicated how well the facility can perform for short-baseline oscillation searches and show its potential for a neutrino interaction physics program. Finally, we comment on the performance potential of the "Neo-conventional" muon neutrino beam optimized for long- baseline neutrino-oscillation physics.« less

New neutrino physics and the altered shapes of solar neutrino spectra

NASA Astrophysics Data System (ADS)

Lopes, Ilídio

2017-01-01

Neutrinos coming from the Sun's core have been measured with high precision, and fundamental neutrino oscillation parameters have been determined with good accuracy. In this work, we estimate the impact that a new neutrino physics model, the so-called generalized Mikheyev-Smirnov-Wolfenstein (MSW) oscillation mechanism, has on the shape of some of leading solar neutrino spectra, some of which will be partially tested by the next generation of solar neutrino experiments. In these calculations, we use a high-precision standard solar model in good agreement with helioseismology data. We found that the neutrino spectra of the different solar nuclear reactions of the pp chains and carbon-nitrogen-oxygen cycle have quite distinct sensitivities to the new neutrino physics. The He P and 8B neutrino spectra are the ones in which their shapes are more affected when neutrinos interact with quarks in addition to electrons. The shapes of the 15O and 17F neutrino spectra are also modified, although in these cases the impact is much smaller. Finally, the impact in the shapes of the P P and 13N neutrino spectra is practically negligible.

Interplay of pathogenic forms of human tau with different autophagic pathways.

PubMed

Caballero, Benjamin; Wang, Yipeng; Diaz, Antonio; Tasset, Inmaculada; Juste, Yves Robert; Stiller, Barbara; Mandelkow, Eva-Maria; Mandelkow, Eckhard; Cuervo, Ana Maria

2018-02-01

Loss of neuronal proteostasis, a common feature of the aging brain, is accelerated in neurodegenerative disorders, including different types of tauopathies. Aberrant turnover of tau, a microtubule-stabilizing protein, contributes to its accumulation and subsequent toxicity in tauopathy patients' brains. A direct toxic effect of pathogenic forms of tau on the proteolytic systems that normally contribute to their turnover has been proposed. In this study, we analyzed the contribution of three different types of autophagy, macroautophagy, chaperone-mediated autophagy, and endosomal microautophagy to the degradation of tau protein variants and tau mutations associated with this age-related disease. We have found that the pathogenic P301L mutation inhibits degradation of tau by any of the three autophagic pathways, whereas the risk-associated tau mutation A152T reroutes tau for degradation through a different autophagy pathway. We also found defective autophagic degradation of tau when using mutations that mimic common posttranslational modifications in tau or known to promote its aggregation. Interestingly, although most mutations markedly reduced degradation of tau through autophagy, the step of this process preferentially affected varies depending on the type of tau mutation. Overall, our studies unveil a complex interplay between the multiple modifications of tau and selective forms of autophagy that may determine its physiological degradation and its faulty clearance in the disease context. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Tau proteins in the cerebrospinal fluid of patients with subacute sclerosing panencephalitis.

PubMed

Yuksel, Deniz; Yilmaz, Deniz; Uyar, Neval Y; Senbil, Nesrin; Gurer, Yavuz; Anlar, Banu

2010-06-01

Neurodegenerative diseases characterized by cytoskeletal deformation and neurofibrillary tangles are associated with altered levels of tau and related proteins in cerebrospinal fluid (CSF). Neuronal or glial fibrillary tangles have been shown in 20% of subacute sclerosing panencephalitis (SSPE) patients. We therefore investigated CSF samples from 60 newly diagnosed SSPE and 31 neurological control patients for total tau (t-tau), phosphorylated tau (p-tau), and S100-B levels by ELISA. There was no difference between patient and control groups in t-tau and S100-B levels. p-Tau was lower in the SSPE group (p=0.009). Past history of measles infection, measles immunization status, latent period between measles and onset of SSPE, duration of symptoms, frequency of myoclonia, neurological deficit index, stage and progression rate of the disease, CSF glucose levels and cell counts, CSF and serum measles IgG titer, distribution of lesions on brain magnetic resonance imaging were not related to t-tau, p-tau and S100-B levels. Mental status and age were negatively correlated with t-tau, and male gender and EEG abnormalities were associated with higher t-tau levels. The levels of tau proteins in our patients suggest there is no, or only scarce and immature, neurofibrillary tangle formation in SSPE. Autopsy studies showing neurofibrillary tangles might have examined older patients with longer disease and more parenchymal involvement. Copyright (c) 2009 Elsevier B.V. All rights reserved.

Physics of neutrino flavor transformation through matter–neutrino resonances

DOE PAGES

Wu, Meng -Ru; Duan, Huaiyu; Qian, Yong -Zhong

2015-11-17

In astrophysical environments such as core-collapse supernovae and neutron star–neutron star or neutron star–black hole mergers where dense neutrino media are present, matter–neutrino resonances (MNRs) can occur when the neutrino propagation potentials due to neutrino–electron and neutrino–neutrino for-ward scattering nearly cancel each other. We show that neutrino flavor transformation through MNRs can be explained by multiple adiabatic solutions similar to the Mikheyev–Smirnov–Wolfenstein mecha-nism. As a result, we find that for the normal neutrino mass hierarchy, neutrino flavor evolution through MNRs can be sensitive to the shape of neutrino spectra and the adiabaticity of the system, but such sensitivity is absentmore » for the inverted hierarchy.« less

A Search for Neutrinos from Fast Radio Bursts with IceCube

NASA Astrophysics Data System (ADS)

Fahey, Samuel; Kheirandish, Ali; Vandenbroucke, Justin; Xu, Donglian

2017-08-01

We present a search for neutrinos in coincidence in time and direction with four fast radio bursts (FRBs) detected by the Parkes and Green Bank radio telescopes during the first year of operation of the complete IceCube Neutrino Observatory (2011 May through 2012 May). The neutrino sample consists of 138,322 muon neutrino candidate events, which are dominated by atmospheric neutrinos and atmospheric muons but also contain an astrophysical neutrino component. Considering only neutrinos detected on the same day as each FRB, zero IceCube events were found to be compatible with the FRB directions within the estimated 99% error radius of the neutrino directions. Based on the non-detection, we present the first upper limits on the neutrino fluence from FRBs.

REVIEWS OF TOPICAL PROBLEMS: Ultrahigh-energy neutrinos from astrophysical sources and superheavy particle decays

NASA Astrophysics Data System (ADS)

Ryabov, Vladimir A.

2006-09-01

Problems in the fields of neutrino astronomy and ultrahigh-energy astrophysics are reviewed. Neutrino fluxes produced in various astrophysical sources (bottom-up acceleration scenarios) and resulting from the decay of superheavy particles (top-down scenarios) are considered. Neutrino oscillation processes and the absorption and regeneration of neutrinos inside the earth are analyzed and some other factors affecting the intensity and flavor composition of astrophysical neutrino fluxes are discussed. Details of ultrahigh-energy neutrino interactions are discussed within the Standard Model, as well as using nonstandard scenarios predicting an anomalous increase in the inelastic neutrino-nucleon cross section. Ultrahigh-energy neutrino detection techniques currently in use in new-generation neutrino telescopes and cosmic ray detectors are also discussed.

Pathological conformations involving the amino terminus of tau occur early in Alzheimer’s disease and are differentially detected by monoclonal antibodies

PubMed Central

Combs, Benjamin; Hamel, Chelsey; Kanaan, Nicholas M.

2016-01-01

Conformational changes involving the amino terminus of the tau protein are among the earliest alterations associated with tau pathology in Alzheimer’s disease and other tauopathies. This region of tau contains a phosphatase-activating domain (PAD) that is aberrantly exposed in pathological forms of the protein, an event that is associated with disruptions in anterograde fast axonal transport. We utilized four antibodies that recognize the amino terminus of tau, TNT1, TNT2 (a novel antibody), Tau12, and Tau13, to further study this important region. Using scanning alanine mutations in recombinant tau proteins, we refined the epitopes of each antibody. We examined the antibodies’ relative abilities to specifically label pathological tau in non-denaturing and denaturing assays to gain insight into some of the mechanistic details of PAD exposure. We then determined the pattern of tau pathology labeled by each antibody in human hippocampal sections at various disease stages in order to characterize PAD exposure in the context of disease progression. The characteristics of reactivity for the antibodies fell into two groups. TNT1 and TNT2 recognized epitopes within amino acids 7–12 and specifically identified recombinant tau aggregates and pathological tau from Alzheimer’s disease brains in a conformation-dependent manner. These antibodies labeled early pre-tangle pathology from neurons in early Braak stages and colocalized with thiazine red, a marker of fibrillar pathology, in classic neurofibrillary tangles. However, late tangles were negative for TNT1 and TNT2 indicating a loss of the epitope in later stages of tangle evolution. In contrast, Tau12 and Tau13 both identified discontinuous epitopes in the amino terminus and were unable to differentiate between normal and pathological tau in biochemical and tissue immunohistological assays. Despite the close proximity of these epitopes, the antibodies demonstrated remarkably different abilities to identify pathological changes in tau indicating that detection of conformational alterations involving PAD exposure is not achieved by all N-terminal tau antibodies and that a relatively discrete region of the N-terminus (i.e., amino acids 7–12, the TNT1 and TNT2 epitope) is central to the differences between normal and pathological tau. The appearance of PAD in early tau pathology and its disappearance in late-stage tangles suggest that toxic forms of tau are associated with the earliest forms of tau deposits. Collectively, these findings demonstrate that the TNT antibodies are useful markers for early conformational display of PAD and provide information regarding conformational changes that have potential implications in the toxic mechanisms of tau pathology. PMID:27260838

Ultrastructural characteristics of tau filaments in tauopathies: immuno-electron microscopic demonstration of tau filaments in tauopathies.

PubMed

Arima, Kunimasa

2006-10-01

The microtubule-associated protein tau aggregates into filaments in the form of neurofibrillary tangles, neuropil threads and argyrophilic grains in neurons, in the form of variable astrocytic tangles in astrocytes and in the form of coiled bodies and argyrophilic threads in oligodendrocytes. These tau filaments may be classified into two types, straight filaments or tubules with 9-18 nm diameters and "twisted ribbons" composed of two parallel aligned components. In the same disease, the fine structure of tau filaments in glial cells roughly resembles that in neurons. In sporadic tauopathies, individual tau filaments show characteristic sizes, shapes and arrangements, and therefore contribute to neuropathologic differential diagnosis. In frontotemporal dementias caused by tau gene mutations, variable filamentous profiles were observed in association with mutation sites and insoluble tau isoforms, including straight filaments or tubules, paired helical filament-like filaments, and twisted ribbons. Pre-embedding immunoelectron microscopic studies were carried out using anti-3-repeat tau and anti-4-repeat tau specific antibodies, RD3 and RD4. Straight tubules in neuronal and astrocytic Pick bodies were immunolabeled by the anti-3-repeat tau antibody. The anti-4-repeat tau antibody recognized abnormal tubules comprising neurofibrillary tangles, coiled bodies and argyrophilic threads in progressive supranuclear palsy (PSP) and corticobasal degeneration. In the pre-embedding immunoelectron microscopic study using the phosphorylated tau AT8 antibody, tuft-shaped astrocytes of PSP were found to be composed of bundles of abnormal tubules in processes and perikarya of protoplasmic astrocytes. In this study, the 3-repeat tau or 4-repeat tau epitope was detected in situ at the ultrastructural level in abnormal tubules in representative pathological lesions in Pick's disease, PSP and corticobasal degeneration.

Direct force measurements reveal that protein Tau confers short-range attractions and isoform-dependent steric stabilization to microtubules

PubMed Central

Chung, Peter J.; Choi, Myung Chul; Miller, Herbert P.; Feinstein, H. Eric; Raviv, Uri; Li, Youli; Wilson, Leslie; Feinstein, Stuart C.; Safinya, Cyrus R.

2015-01-01

Microtubules (MTs) are hollow cytoskeletal filaments assembled from αβ-tubulin heterodimers. Tau, an unstructured protein found in neuronal axons, binds to MTs and regulates their dynamics. Aberrant Tau behavior is associated with neurodegenerative dementias, including Alzheimer’s. Here, we report on a direct force measurement between paclitaxel-stabilized MTs coated with distinct Tau isoforms by synchrotron small-angle X-ray scattering (SAXS) of MT-Tau mixtures under osmotic pressure (P). In going from bare MTs to MTs with Tau coverage near the physiological submonolayer regime (Tau/tubulin-dimer molar ratio; ΦTau = 1/10), isoforms with longer N-terminal tails (NTTs) sterically stabilized MTs, preventing bundling up to PB ∼ 10,000–20,000 Pa, an order of magnitude larger than bare MTs. Tau with short NTTs showed little additional effect in suppressing the bundling pressure (PB ∼ 1,000–2,000 Pa) over the same range. Remarkably, the abrupt increase in PB observed for longer isoforms suggests a mushroom to brush transition occurring at 1/13 < ΦTau < 1/10, which corresponds to MT-bound Tau with NTTs that are considerably more extended than SAXS data for Tau in solution indicate. Modeling of Tau-mediated MT–MT interactions supports the hypothesis that longer NTTs transition to a polyelectrolyte brush at higher coverages. Higher pressures resulted in isoform-independent irreversible bundling because the polyampholytic nature of Tau leads to short-range attractions. These findings suggest an isoform-dependent biological role for regulation by Tau, with longer isoforms conferring MT steric stabilization against aggregation either with other biomacromolecules or into tight bundles, preventing loss of function in the crowded axon environment. PMID:26542680

Charged Cosmic Rays and Neutrinos

NASA Astrophysics Data System (ADS)

Kachelrieß, M.

2013-04-01

High-energy neutrino astronomy has grown up, with IceCube as one of its main experiments having sufficient sensitivity to test "vanilla" models of astrophysical neutrinos. I review predictions of neutrino fluxes as well as the status of cosmic ray physics. I comment also briefly on an improvement of the Fermi-LAT limit for cosmogenic neutrinos and on the two neutrino events presented by IceCube first at "Neutrino 2012".

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

Signature of heavy sterile neutrinos at CEPC

NASA Astrophysics Data System (ADS)

Liao, Wei; Wu, Xiao-Hong

2018-03-01

We study the production of heavy sterile neutrino N , e+e-→N ν (ν ¯), at the Circular Electron Positron Collider (CEPC) and its l j j signal in its decay to three charged fermions. We study background events for this process which are mainly events coming from W pair production. We study the production of a single heavy sterile neutrino and the sensitivity of CEPC to the mixing of the sterile neutrino with active neutrinos. We study the production of two degenerate heavy sterile neutrinos in a low energy seesaw model by taking into account the constraints on mixings of sterile neutrinos from the neutrinoless double β decay experiment and the masses and mixings of active neutrinos. We show that CEPC under proposal has a good sensitivity to the mixing of sterile neutrinos with active neutrinos for a mass of a sterile neutrino around 100 GeV.

Constraints and tests of the OPERA superluminal neutrinos.

PubMed

Bi, Xiao-Jun; Yin, Peng-Fei; Yu, Zhao-Huan; Yuan, Qiang

2011-12-09

The superluminal neutrinos detected by OPERA indicate Lorentz invariance violation (LIV) of the neutrino sector at the order of 10(-5). We study the implications of the result in this work. We find that such a large LIV implied by OPERA data will make the neutrino production process π → μ + ν(μ) kinematically forbidden for a neutrino energy greater than about 5 GeV. The OPERA detection of neutrinos at 40 GeV can constrain the LIV parameter to be smaller than 3×10(-7). Furthermore, the neutrino decay in the LIV framework will modify the neutrino spectrum greatly. The atmospheric neutrino spectrum measured by the IceCube Collaboration can constrain the LIV parameter to the level of 10(-12). The future detection of astrophysical neutrinos of galactic sources is expected to be able to give an even stronger constraint on the LIV parameter of neutrinos.

Constraints and Tests of the OPERA Superluminal Neutrinos

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bi Xiaojun; Yin Pengfei; Yu Zhaohuan

The superluminal neutrinos detected by OPERA indicate Lorentz invariance violation (LIV) of the neutrino sector at the order of 10{sup -5}. We study the implications of the result in this work. We find that such a large LIV implied by OPERA data will make the neutrino production process {pi}{yields}{mu}+{nu}{sub {mu}} kinematically forbidden for a neutrino energy greater than about 5 GeV. The OPERA detection of neutrinos at 40 GeV can constrain the LIV parameter to be smaller than 3x10{sup -7}. Furthermore, the neutrino decay in the LIV framework will modify the neutrino spectrum greatly. The atmospheric neutrino spectrum measured bymore » the IceCube Collaboration can constrain the LIV parameter to the level of 10{sup -12}. The future detection of astrophysical neutrinos of galactic sources is expected to be able to give an even stronger constraint on the LIV parameter of neutrinos.« less

Recent Results from the T2K Experiment

NASA Astrophysics Data System (ADS)

Abe, K.; Abgrall, N.; Aihara, H.; Akiri, T.; Andreopoulos, C.; Aoki, S.; Ariga, A.; Ariga, T.; Assylbekov, S.; Autiero, D.; Barbi, M.; Barker, G. J.; Barr, G.; Bass, M.; Batkiewicz, M.; Bay, F.; Bentham, S. W.; Berardi, V.; Berger, B. E.; Berkman, S.; Bertram, I.; Bhadra, S.; Blaszczyk, F. D. M.; Blondel, A.; Bojechko, C.; Boyd, S. B.; Brailsford, D.; Bravar, A.; Bronner, C.; Buchanan, N.; Calland, R. G.; Caravaca Rodríguez, J.; Cartwright, S. L.; Castillo, R.; Catanesi, M. G.; Cervera, A.; Cherdack, D.; Christodoulou, G.; Clifton, A.; Coleman, J.; Coleman, S. J.; Collazuol, G.; Connolly, K.; Cremonesi, L.; Curioni, A.; Dabrowska, A.; Danko, I.; Das, R.; Davis, S.; de Perio, P.; De Rosa, G.; Dealtry, T.; Dennis, S. R.; Densham, C.; Di Lodovico, F.; Di Luise, S.; Drapier, O.; Duboyski, T.; Dufour, F.; Dumarchez, J.; Dytman, S.; Dziewiecki, M.; Emery, S.; Ereditato, A.; Escudero, L.; Finch, A. J.; Frank, E.; Friend, M.; Fujii, Y.; Fukuda, Y.; Furmanski, A. P.; Galymov, V.; Gaudin, A.; Giffin, S.; Giganti, C.; Gilje, K.; Golan, T.; Gomez-Cadenas, J. J.; Gonin, M.; Grant, N.; Gudin, D.; Hadley, D. R.; Haesler, A.; Haigh, M. D.; Hamilton, P.; Hansen, D.; Hara, T.; Hartz, M.; Hasegawa, T.; Hastings, N. C.; Hayato, Y.; Hearty, C.; Helmer, R. L.; Hierholzer, M.; Hignight, J.; Hillairet, A.; Himmel, A.; Hiraki, T.; Hirota, S.; Holeczek, J.; Horikawa, S.; Huang, K.; Ichikawa, A. K.; Ieki, K.; Ieva, M.; Ikeda, M.; Imber, J.; Insler, J.; Irvine, T. J.; Ishida, T.; Ishii, T.; Ives, S. J.; Iyogi, K.; Izmaylov, A.; Jacob, A.; Jamieson, B.; Johnson, R. A.; Jo, J. H.; Jonsson, P.; Joo, K. K.; Jung, C. K.; Kaboth, A. C.; Kajita, T.; Kakuno, H.; Kameda, J.; Kanazawa, Y.; Karlen, D.; Karpikov, I.; Kearns, E.; Khabibullin, M.; Khotjantsev, A.; Kielczewska, D.; Kikawa, T.; Kilinski, A.; Kim, J.; Kim, S. B.; Kisiel, J.; Kitching, P.; Kobayashi, T.; Kogan, G.; Kolaceke, A.; Konaka, A.; Kormos, L. L.; Korzenev, A.; Koseki, K.; Koshio, Y.; Kreslo, I.; Kropp, W.; Kubo, H.; Kudenko, Y.; Kumaratunga, S.; Kurjata, R.; Kutter, T.; Lagoda, J.; Laihem, K.; Laveder, M.; Lawe, M.; Lazos, M.; Lee, K. P.; Licciardi, C.; Lim, I. T.; Lindner, T.; Lister, C.; Litchfield, R. P.; Longhin, A.; Lopez, G. D.; Ludovici, L.; Macaire, M.; Magaletti, L.; Mahn, K.; Malek, M.; Manly, S.; Marino, A. D.; Marteau, J.; Martin, J. F.; Maruyama, T.; Marzec, J.; Masliah, P.; Mathie, E. L.; Matveev, V.; Mavrokoridis, K.; Mazzucato, E.; McCauley, N.; McFarland, K. S.; McGrew, C.; Metelko, C.; Mijakowski, P.; Miller, C. A.; Minamino, A.; Mineev, O.; Mine, S.; Missert, A.; Miura, M.; Monfregola, L.; Moriyama, S.; Mueller, Th. A.; Murakami, A.; Murdoch, M.; Murphy, S.; Myslik, J.; Nagasaki, T.; Nakadaira, T.; Nakahata, M.; Nakai, T.; Nakamura, K.; Nakayama, S.; Nakaya, T.; Nakayoshi, K.; Nielsen, C.; Nirkko, M.; Nishikawa, K.; Nishimura, Y.; O'Keeffe, H. M.; Ohta, R.; Okumura, K.; Okusawa, T.; Oryszczak, W.; Oser, S. M.; Otani, M.; Owen, R. A.; Oyama, Y.; Pac, M. Y.; Palladino, V.; Paolone, V.; Payne, D.; Pearce, G. F.; Perevozchikov, O.; Perkin, J. D.; Petrov, Y.; Pinzon Guerra, E. S.; Pistillo, C.; Plonski, P.; Poplawska, E.; Popov, B.; Posiadala, M.; Poutissou, J.-M.; Poutissou, R.; Przewlocki, P.; Quilain, B.; Radicioni, E.; Ratoff, P. N.; Ravonel, M.; Rayner, M. A. M.; Redij, A.; Reeves, M.; Reinherz-Aronis, E.; Retiere, F.; Robert, A.; Rodrigues, P. A.; Rondio, E.; Roth, S.; Rubbia, A.; Ruterbories, D.; Sacco, R.; Sakashita, K.; Sánchez, F.; Scantamburlo, E.; Scholberg, K.; Schwehr, J.; Scott, M.; Seiya, Y.; Sekiguchi, T.; Sekiya, H.; Sgalaberna, D.; Shiozawa, M.; Short, S.; Shustrov, Y.; Sinclair, P.; Smith, B.; Smith, R. J.; Smy, M.; Sobczyk, J. T.; Sobel, H.; Sorel, M.; Southwell, L.; Stamoulis, P.; Steinmann, J.; Still, B.; Suda, Y.; Suzuki, A.; Suzuki, K.; Suzuki, S. Y.; Suzuki, Y.; Szeglowski, T.; Tacik, R.; Tada, M.; Takahashi, S.; Takeda, A.; Takeuchi, Y.; Tanaka, H. A.; Tanaka, M. M.; Taylor, I. J.; Terhorst, D.; Terri, R.; Thompson, L. F.; Thorley, A.; Tobayama, S.; Toki, W.; Tomura, T.; Totsuka, Y.; Touramanis, C.; Tsukamoto, T.; Tzanov, M.; Uchida, Y.; Ueno, K.; Vacheret, A.; Vagins, M.; Vasseur, G.; Wachala, T.; Waldron, A. V.; Walter, C. W.; Wark, D.; Wascko, M. O.; Weber, A.; Wendell, R.; Wilkes, R. J.; Wilking, M. J.; Wilkinson, C.; Williamson, Z.; Wilson, J. R.; Wilson, R. J.; Wongjirad, T.; Yamada, Y.; Yamamoto, K.; Yanagisawa, C.; Yen, S.; Yershov, N.; Yokoyama, M.; Yuan, T.; Zalewska, A.; Zalipska, J.; Zambelli, L.; Zaremba, K.; Ziembicki, M.; Zimmerman, E. D.; Zito, M.; Żmuda, J.

2014-01-01

The Tokai to Kamioka (T2K) experiment studies neutrino oscillations using a beam of muon neutrinos produced by an accelerator. The neutrinos travel from J-PARC on the east coast of Japan and are detected 295 kilometers further away in the Super-Kamiokande detector. A complex of near detectors located 280 meters away from the neutrino production target is used to better characterize the neutrino beam and reduce systematic uncertainties. The experiment aims at measuring electronic neutrino appearance (νμ →νe oscillation) to measure the neutrino mixing angle θ13, and muon neutrino disappearance to measure the neutrino mixing angle θ23 and mass splitting | Δ m322 |. We report here electron neutrino appearance results using three years of data, recorded until the 2012 summer, as well as muon neutrino disappearance results based on the data coming from the first two years of the experiment.

Single-molecule tracking of tau reveals fast kiss-and-hop interaction with microtubules in living neurons

PubMed Central

Janning, Dennis; Igaev, Maxim; Sündermann, Frederik; Brühmann, Jörg; Beutel, Oliver; Heinisch, Jürgen J.; Bakota, Lidia; Piehler, Jacob; Junge, Wolfgang; Brandt, Roland

2014-01-01

The microtubule-associated phosphoprotein tau regulates microtubule dynamics and is involved in neurodegenerative diseases collectively called tauopathies. It is generally believed that the vast majority of tau molecules decorate axonal microtubules, thereby stabilizing them. However, it is an open question how tau can regulate microtubule dynamics without impeding microtubule-dependent transport and how tau is also available for interactions other than those with microtubules. Here we address this apparent paradox by fast single-molecule tracking of tau in living neurons and Monte Carlo simulations of tau dynamics. We find that tau dwells on a single microtubule for an unexpectedly short time of ∼40 ms before it hops to the next. This dwell time is 100-fold shorter than previously reported by ensemble measurements. Furthermore, we observed by quantitative imaging using fluorescence decay after photoactivation recordings of photoactivatable GFP–tagged tubulin that, despite this rapid dynamics, tau is capable of regulating the tubulin–microtubule balance. This indicates that tau's dwell time on microtubules is sufficiently long to influence the lifetime of a tubulin subunit in a GTP cap. Our data imply a novel kiss-and-hop mechanism by which tau promotes neuronal microtubule assembly. The rapid kiss-and-hop interaction explains why tau, although binding to microtubules, does not interfere with axonal transport. PMID:25165145

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Papasozomenos, S.C.; Yuan Su

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 themore » 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.« less

Effects of neutrino oscillations on nucleosynthesis and neutrino signals for an 18 M⊙ supernova model

NASA Astrophysics Data System (ADS)

Wu, Meng-Ru; Qian, Yong-Zhong; Martínez-Pinedo, Gabriel; Fischer, Tobias; Huther, Lutz

2015-03-01

In this paper, we explore the effects of neutrino flavor oscillations on supernova nucleosynthesis and on the neutrino signals. Our study is based on detailed information about the neutrino spectra and their time evolution from a spherically symmetric supernova model for an 18 M⊙ progenitor. We find that collective neutrino oscillations are not only sensitive to the detailed neutrino energy and angular distributions at emission, but also to the time evolution of both the neutrino spectra and the electron density profile. We apply the results of neutrino oscillations to study the impact on supernova nucleosynthesis and on the neutrino signals from a Galactic supernova. We show that in our supernova model, collective neutrino oscillations enhance the production of rare isotopes 138La and 180Ta but have little impact on the ν p -process nucleosynthesis. In addition, the adiabatic Mikheyev-Smirnov-Wolfenstein flavor transformation, which occurs in the C /O and He shells of the supernova, may affect the production of light nuclei such as 7Li and 11B. For the neutrino signals, we calculate the rate of neutrino events in the Super-Kamiokande detector and in a hypothetical liquid argon detector. Our results suggest the possibility of using the time profiles of the events in both detectors, along with the spectral information of the detected neutrinos, to infer the neutrino mass hierarchy.

Harnessing the immune system for treatment and detection of tau pathology.

PubMed

Congdon, Erin E; Krishnaswamy, Senthilkumar; Sigurdsson, Einar M

2014-01-01

The tau protein is an attractive target for therapy and diagnosis. We started a tau immunotherapy program about 13 years ago and have since demonstrated that active and passive immunotherapies diminish tau pathology and improve function, including cognition, in different mouse models. These findings have been confirmed and extended by several groups. We routinely detect neuronal, and to a lesser extent microglial, antibody uptake correlating with tau pathology. Antibodies bind tau aggregates in the endosomal/lysosomal system, enhancing clearance presumably by promoting their disassembly. Extracellular clearance has recently been shown by others, using antibodies that apparently are not internalized. As most pathological tau is neuronal, intracellular targeting may be more efficacious. However, extracellular tau may be more accessible to antibodies, with tau-antibody complexes a target for microglial phagocytosis. The extent of involvement of each pathway may depend on numerous factors including antibody properties, degree of pathology, and experimental model. On the imaging front, multiple tau ligands derived from β-sheet dyes have been developed by several groups, some with promising results in clinical PET tests. Postmortem analysis should clarify their tau specificity, as in theory and based on histological staining, those are likely to have some affinity for various amyloids. We are developing antibody-derived tau probes that should be more specific, and have in mouse models shown in vivo detection and binding to pathological tau after peripheral injection. These are exciting times for research on tau therapies and diagnostic agents that hopefully can be applied to humans in the near future.

DOPA Decarboxylase Modulates Tau Toxicity.

PubMed

Kow, Rebecca L; Sikkema, Carl; Wheeler, Jeanna M; Wilkinson, Charles W; Kraemer, Brian C

2018-03-01

The microtubule-associated protein tau accumulates into toxic aggregates in multiple neurodegenerative diseases. We found previously that loss of D 2 -family dopamine receptors ameliorated tauopathy in multiple models including a Caenorhabditis elegans model of tauopathy. To better understand how loss of D 2 -family dopamine receptors can ameliorate tau toxicity, we screened a collection of C. elegans mutations in dopamine-related genes (n = 45) for changes in tau transgene-induced behavioral defects. These included many genes responsible for dopamine synthesis, metabolism, and signaling downstream of the D 2 receptors. We identified one dopamine synthesis gene, DOPA decarboxylase (DDC), as a suppressor of tau toxicity in tau transgenic worms. Loss of the C. elegans DDC gene, bas-1, ameliorated the behavioral deficits of tau transgenic worms, reduced phosphorylated and detergent-insoluble tau accumulation, and reduced tau-mediated neuron loss. Loss of function in other genes in the dopamine and serotonin synthesis pathways did not alter tau-induced toxicity; however, their function is required for the suppression of tau toxicity by bas-1. Additional loss of D 2 -family dopamine receptors did not synergize with bas-1 suppression of tauopathy phenotypes. Loss of the DDC bas-1 reduced tau-induced toxicity in a C. elegans model of tauopathy, while loss of no other dopamine or serotonin synthesis genes tested had this effect. Because loss of activity upstream of DDC could reduce suppression of tau by DDC, this suggests the possibility that loss of DDC suppresses tau via the combined accumulation of dopamine precursor levodopa and serotonin precursor 5-hydroxytryptophan. Published by Elsevier Inc.

Altered Body Weight Regulation in CK1ε Null and tau Mutant Mice on Regular Chow and High Fat Diets

PubMed Central

Zhou, Lili; Summa, Keith C.; Olker, Christopher; Vitaterna, Martha H.; Turek, Fred W.

2016-01-01

Disruption of circadian rhythms results in metabolic dysfunction. Casein kinase 1 epsilon (CK1ε) is a canonical circadian clock gene. Null and tau mutations in CK1ε show distinct effects on circadian period. To investigate the role of CK1ε in body weight regulation under both regular chow (RC) and high fat (HF) diet conditions, we examined body weight on both RC and HF diets in CK1ε −/− and CK1ε tau/tau mice on a standard 24 hr light-dark (LD) cycle. Given the abnormal entrainment of CK1ε tau/tau mice on a 24 hr LD cycle, a separate set of CK1ε tau/tau mice were tested under both diet conditions on a 20 hr LD cycle, which more closely matches their endogenous period length. On the RC diet, both CK1ε −/− and CK1ε tau/tau mutants on a 24 hr LD cycle and CK1ε tau/tau mice on a 20 hr LD cycle exhibited significantly lower body weights, despite similar overall food intake and activity levels. On the HF diet, CK1ε tau/tau mice on a 20 hr LD cycle were protected against the development of HF diet-induced excess weight gain. These results provide additional evidence supporting a link between circadian rhythms and energy regulation at the genetic level, particularly highlighting CK1ε involved in the integration of circadian biology and metabolic physiology. PMID:27144030

A Novel MAPT Mutation, G55R, in a Frontotemporal Dementia Patient Leads to Altered Tau Function

PubMed Central

Guzman, Elmer; Barczak, Anna; Chodakowska-Żebrowska, Małgorzata; Barcikowska, Maria; Feinstein, Stuart

2013-01-01

Over two dozen mutations in the gene encoding the microtubule associated protein tau cause a variety of neurodegenerative dementias known as tauopathies, including frontotemporal dementia (FTD), PSP, CBD and Pick's disease. The vast majority of these mutations map to the C-terminal region of tau possessing microtubule assembly and microtubule dynamics regulatory activities as well as the ability to promote pathological tau aggregation. Here, we describe a novel and non-conservative tau mutation (G55R) mapping to an alternatively spliced exon encoding part of the N-terminal region of the protein in a patient with the behavioral variant of FTD. Although less well understood than the C-terminal region of tau, the N-terminal region can influence both MT mediated effects as well as tau aggregation. The mutation changes an uncharged glycine to a basic arginine in the midst of a highly conserved and very acidic region. In vitro, 4-repeat G55R tau nucleates microtubule assembly more effectively than wild-type 4-repeat tau; surprisingly, this effect is tau isoform specific and is not observed in a 3-repeat G55R tau versus 3-repeat wild-type tau comparison. In contrast, the G55R mutation has no effect upon the abilities of tau to regulate MT growing and shortening dynamics or to aggregate. Additionally, the mutation has no effect upon kinesin translocation in a microtubule gliding assay. Together, (i) we have identified a novel tau mutation mapping to a mutation deficient region of the protein in a bvFTD patient, and (ii) the G55R mutation affects the ability of tau to nucleate microtubule assembly in vitro in a 4-repeat tau isoform specific manner. This altered capability could markedly affect in vivo microtubule function and neuronal cell biology. We consider G55R to be a candidate mutation for bvFTD since additional criteria required to establish causality are not yet available for assessment. PMID:24086739

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.

Low-energy neutrinos

NASA Astrophysics Data System (ADS)

Ludhova, Livia

2016-05-01

There exist several kinds of sources emitting neutrinos in the MeV energy range. These low-energy neutrinos from different sources can be often detected by the same multipurpose detectors. The status-of-art of the field of solar neutrinos, geoneutrinos, and the search for sterile neutrino with artificial neutrino sources is provided here; other neutrino sources, as for example reactor or high-energy neutrinos, are described elsewhere. For each of these three fields, the present-day motivation and open questions, as well as the latest experimental results and future perspectives are discussed.

Sterile neutrino dark matter production

NASA Astrophysics Data System (ADS)

Gorbunov, Dmitry

2017-10-01

Sterile neutrinos provide active neutrinos with masses and mixing, and hence is one of the well-motivated candidate for dark matter. We discuss the sterile neutrino production mechanisms operating in the early Universe and show that additional scalar coupled to sterile neutrino can significantly change the situation, making moderate sterile-neutrino mixing and small sterile neutrino masses consistent with current cosmological and astrophysical bounds. Further searches for a narrow line in galactic X-rays and even direct searches for keV-scale sterile neutrinos in particle physics experiments can probe the suggested setup.

Long-Baseline Neutrino Experiments

DOE PAGES

Diwan, M. V.; Galymov, V.; Qian, X.; ...

2016-10-19

We review long-baseline neutrino experiments in which neutrinos are detected after traversing macroscopic distances. Over such distances neutrinos have been found to oscillate among flavor states. Experiments with solar, atmospheric, reactor, and accelerator neutrinos have resulted in a coherent picture of neutrino masses and mixing of the three known flavor states. We will summarize the current best knowledge of neutrino parameters and phenomenology with our focus on the evolution of the experimental technique. We will proceed from the rst evidence produced by astrophysical neutrino sources to the current open questions and the goals of future research

Low-energy (anti)neutrino physics with Borexino: Neutrinos from the primary proton-proton fusion process in the Sun

NASA Astrophysics Data System (ADS)

Mosteiro, P.; Bellini, G.; Benziger, J.; Bick, D.; Bonfini, G.; Bravo, D.; Caccianiga, B.; Cadonati, L.; Calaprice, F.; Caminata, A.; Cavalcante, P.; Chavarría, Á.; Chepurnov, A.; D'Angelo, D.; Davini, S.; Derbin, A.; Empl, A.; Etenko, A.; Fomenko, K.; Franco, D.; Gabriele, F.; Galbiati, C.; Gazzana, S.; Ghiano, C.; Giammarchi, M.; Göger-Neff, M.; Goretti, A.; Gromov, M.; Hagner, C.; Hungerford, E.; Ianni, Al.; Ianni, An.; Kobychev, V.; Korablëv, D.; Korga, G.; Kryn, D.; Laubenstein, M.; Lehnert, B.; Lewke, T.; Litvinovich, E.; Lombardi, F.; Lombardi, P.; Ludhova, L.; Lukyanchenko, G.; Machulin, I.; Manecki, S.; Maneschg, W.; Marcocci, S.; Meindl, Q.; Meroni, E.; Meyer, M.; Miramonti, L.; Misiaszek, M.; Montuschi, M.; Muratova, V.; Oberauer, L.; Obolensky, M.; Ortica, F.; Otis, K.; Pallavicini, M.; Papp, L.; Perasso, L.; Pocar, A.; Ranucci, G.; Razeto, A.; Re, A.; Romani, A.; Rossi, N.; Saldanha, R.; Salvo, C.; Schönert, S.; Simgen, H.; Skorokhvatov, M.; Smirnov, O.; Sotnikov, A.; Sukhotin, S.; Suvorov, Y.; Tartaglia, R.; Testera, G.; Vignaud, D.; Vogelaar, R. B.; von Feilitzsch, F.; Wang, H.; Winter, J.; Wojcik, M.; Wright, A.; Wurm, M.; Zaimidoroga, O.; Zavatarelli, S.; Zuber, K.; Zuzel, G.

2015-08-01

The Sun is fueled by a series of nuclear reactions that produce the energy that makes it shine. The primary reaction is the fusion of two protons into a deuteron, a positron and a neutrino. These neutrinos constitute the vast majority of neutrinos reaching Earth, providing us with key information about what goes on at the core of our star. Several experiments have now confirmed the observation of neutrino oscillations by detecting neutrinos from secondary nuclear processes in the Sun; this is the first direct spectral measurement of the neutrinos from the keystone proton-proton fusion. This observation is a crucial step towards the completion of the spectroscopy of pp-chain neutrinos, as well as further validation of the LMA-MSW model of neutrino oscillations.

Limiting neutrino magnetic moments with Borexino Phase-II solar neutrino data

NASA Astrophysics Data System (ADS)

Agostini, M.; Altenmüller, K.; Appel, S.; Atroshchenko, V.; Bagdasarian, Z.; Basilico, D.; Bellini, G.; Benziger, J.; Bick, D.; Bonfini, G.; Bravo, D.; Caccianiga, B.; Calaprice, F.; Caminata, A.; Caprioli, S.; Carlini, M.; Cavalcante, P.; Chepurnov, A.; Choi, K.; Collica, L.; D'Angelo, D.; Davini, S.; Derbin, A.; Ding, X. F.; Di Ludovico, A.; Di Noto, L.; Drachnev, I.; Fomenko, K.; Formozov, A.; Franco, D.; Froborg, F.; Gabriele, F.; Galbiati, C.; Ghiano, C.; Giammarchi, M.; Goretti, A.; Gromov, M.; Guffanti, D.; Hagner, C.; Houdy, T.; Hungerford, E.; Ianni, Aldo; Ianni, Andrea; Jany, A.; Jeschke, D.; Kobychev, V.; Korablev, D.; Korga, G.; Kryn, D.; Laubenstein, M.; Litvinovich, E.; Lombardi, F.; Lombardi, P.; Ludhova, L.; Lukyanchenko, G.; Lukyanchenko, L.; Machulin, I.; Manuzio, G.; Marcocci, S.; Martyn, J.; Meroni, E.; Meyer, M.; Miramonti, L.; Misiaszek, M.; Muratova, V.; Neumair, B.; Oberauer, L.; Opitz, B.; Orekhov, V.; Ortica, F.; Pallavicini, M.; Papp, L.; Penek, Ã.-.; Pilipenko, N.; Pocar, A.; Porcelli, A.; Ranucci, G.; Razeto, A.; Re, A.; Redchuk, M.; Romani, A.; Roncin, R.; Rossi, N.; Schönert, S.; Semenov, D.; Skorokhvatov, M.; Smirnov, O.; Sotnikov, A.; Stokes, L. F. F.; Suvorov, Y.; Tartaglia, R.; Testera, G.; Thurn, J.; Toropova, M.; Unzhakov, E.; Vishneva, A.; Vogelaar, R. B.; von Feilitzsch, F.; Wang, H.; Weinz, S.; Wojcik, M.; Wurm, M.; Yokley, Z.; Zaimidoroga, O.; Zavatarelli, S.; Zuber, K.; Zuzel, G.; Borexino Collaboration

2017-11-01

A search for the solar neutrino effective magnetic moment has been performed using data from 1291.5 days exposure during the second phase of the Borexino experiment. No significant deviations from the expected shape of the electron recoil spectrum from solar neutrinos have been found, and a new upper limit on the effective neutrino magnetic moment of μνeff<2.8×10 -11 μB at 90% C.L. has been set using constraints on the sum of the solar neutrino fluxes implied by the radiochemical gallium experiments. Using the limit for the effective neutrino moment, new limits for the magnetic moments of the neutrino flavor states, and for the elements of the neutrino magnetic moments matrix for Dirac and Majorana neutrinos, are derived.

Constraints on decay plus oscillation solutions of the solar neutrino problem

NASA Astrophysics Data System (ADS)

Joshipura, Anjan S.; Massó, Eduard; Mohanty, Subhendra

2002-12-01

We examine the constraints on the nonradiative decay of neutrinos from the observations of solar neutrino experiments. The standard oscillation hypothesis among three neutrinos solves the solar and atmospheric neutrino problems. The decay of a massive neutrino mixed with the electron neutrino results in the depletion of the solar neutrino flux. We introduce neutrino decay in the oscillation hypothesis and demand that decay does not spoil the successful explanation of solar and atmospheric observations. We obtain a lower bound on the ratio of the lifetime over the mass of ν2, τ2/m2>22.7 s/MeV for the Mikheyev-Smirnov-Wolfenstein solution of the solar neutrino problem and τ2/m2>27.8 s/MeV for the vacuum oscillation solution (at 99% C.L.).

No Collective Neutrino Flavor Conversions during the Supernova Accretion Phase

NASA Astrophysics Data System (ADS)

Chakraborty, Sovan; Fischer, Tobias; Mirizzi, Alessandro; Saviano, Ninetta; Tomàs, Ricard

2011-10-01

We perform a dedicated study of the supernova (SN) neutrino flavor evolution during the accretion phase, using results from recent neutrino radiation hydrodynamics simulations. In contrast to what was expected in the presence of only neutrino-neutrino interactions, we find that the multiangle effects associated with the dense ordinary matter suppress collective oscillations. The matter suppression implies that neutrino oscillations will start outside the neutrino decoupling region and therefore will have a negligible impact on the neutrino heating and the explosion dynamics. Furthermore, the possible detection of the next galactic SN neutrino signal from the accretion phase, based on the usual Mikheyev-Smirnov-Wolfenstein effect in the SN mantle and Earth matter effects, can reveal the neutrino mass hierarchy in the case that the mixing angle θ13 is not very small.

No collective neutrino flavor conversions during the supernova accretion phase.

PubMed

Chakraborty, Sovan; Fischer, Tobias; Mirizzi, Alessandro; Saviano, Ninetta; Tomàs, Ricard

2011-10-07

We perform a dedicated study of the supernova (SN) neutrino flavor evolution during the accretion phase, using results from recent neutrino radiation hydrodynamics simulations. In contrast to what was expected in the presence of only neutrino-neutrino interactions, we find that the multiangle effects associated with the dense ordinary matter suppress collective oscillations. The matter suppression implies that neutrino oscillations will start outside the neutrino decoupling region and therefore will have a negligible impact on the neutrino heating and the explosion dynamics. Furthermore, the possible detection of the next galactic SN neutrino signal from the accretion phase, based on the usual Mikheyev-Smirnov-Wolfenstein effect in the SN mantle and Earth matter effects, can reveal the neutrino mass hierarchy in the case that the mixing angle θ(13) is not very small.

Physics prospects of the Jinping neutrino experiment

NASA Astrophysics Data System (ADS)

Beacom, John F.; Chen, Shaomin; Cheng, Jianping; Doustimotlagh, Sayed N.; Gao, Yuanning; Gong, Guanghua; Gong, Hui; Guo, Lei; Han, Ran; He, Hong-Jian; Huang, Xingtao; Li, Jianmin; Li, Jin; Li, Mohan; Li, Xueqian; Liao, Wei; Lin, Guey-Lin; Liu, Zuowei; McDonough, William; Šrámek, Ondřej; Tang, Jian; Wan, Linyan; Wang, Yuanqing; Wang, Zhe; Wang, Zongyi; Wei, Hanyu; Xi, Yufei; Xu, Ye; Xu, Xun-Jie; Yang, Zhenwei; Yao, Chunfa; Yeh, Minfang; Yue, Qian; Zhang, Liming; Zhang, Yang; Zhao, Zhihong; Zheng, Yangheng; Zhou, Xiang; Zhu, Xianglei; Zuber, Kai

2017-02-01

The China Jinping Underground Laboratory (CJPL), which has the lowest cosmic-ray muon flux and the lowest reactor neutrino flux of any laboratory, is ideal to carry out low-energy neutrino experiments. With two detectors and a total fiducial mass of 2000 tons for solar neutrino physics (equivalently, 3000 tons for geo-neutrino and supernova neutrino physics), the Jinping neutrino experiment will have the potential to identify the neutrinos from the CNO fusion cycles of the Sun, to cover the transition phase for the solar neutrino oscillation from vacuum to matter mixing, and to measure the geo-neutrino flux, including the Th/U ratio. These goals can be fulfilled with mature existing techniques. Efforts on increasing the target mass with multi-modular neutrino detectors and on developing the slow liquid scintillator will increase the Jinping discovery potential in the study of solar neutrinos, geo-neutrinos, supernova neutrinos, and dark matter. Supported by the National Natural Science Foundation of China (11235006, 11475093, 11135009, 11375065, 11505301, and 11620101004), the Tsinghua University Initiative Scientific Research Program (20121088035, 20131089288, and 20151080432), the Key Laboratory of Particle & Radiation Imaging (Tsinghua University), the CAS Center for Excellence in Particle Physics (CCEPP), U.S. National Science Foundation Grant PHY-1404311 (Beacom), and U.S. Department of Energy under contract DE-AC02-98CH10886 (Yeh).

Constraints and consequences of reducing small scale structure via large dark matter-neutrino interactions

DOE PAGES

Bertoni, Bridget; Ipek, Seyda; McKeen, David; ...

2015-04-30

Here, cold dark matter explains a wide range of data on cosmological scales. However, there has been a steady accumulation of evidence for discrepancies between simulations and observations at scales smaller than galaxy clusters. One promising way to affect structure formation on small scales is a relatively strong coupling of dark matter to neutrinos. We construct an experimentally viable, simple, renormalizable model with new interactions between neutrinos and dark matter and provide the first discussion of how these new dark matter-neutrino interactions affect neutrino phenomenology. We show that addressing the small scale structure problems requires asymmetric dark matter with amore » mass that is tens of MeV. Generating a sufficiently large dark matter-neutrino coupling requires a new heavy neutrino with a mass around 100 MeV. The heavy neutrino is mostly sterile but has a substantial τ neutrino component, while the three nearly massless neutrinos are partly sterile. This model can be tested by future astrophysical, particle physics, and neutrino oscillation data. Promising signatures of this model include alterations to the neutrino energy spectrum and flavor content observed from a future nearby supernova, anomalous matter effects in neutrino oscillations, and a component of the τ neutrino with mass around 100 MeV.« less

Neutrino Oscillation Physics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kayser, Boris

2012-06-01

To complement the neutrino-physics lectures given at the 2011 International School on Astro Particle Physics devoted to Neutrino Physics and Astrophysics (ISAPP 2011; Varenna, Italy), at the 2011 European School of High Energy Physics (ESHEP 2011; Cheila Gradistei, Romania), and, in modified form, at other summer schools, we present here a written description of the physics of neutrino oscillation. This description is centered on a new way of deriving the oscillation probability. We also provide a brief guide to references relevant to topics other than neutrino oscillation that were covered in the lectures. Neutrinos and photons are by far themore » most abundant elementary particles in the universe. Thus, if we would like to comprehend the universe, we must understand the neutrinos. Of course, studying the neutrinos is challenging, since the only known forces through which these electrically-neutral leptons interact are the weak force and gravity. Consequently, interactions of neutrinos in a detector are very rare events, so that very large detectors and intense neutrino sources are needed to make experiments feasible. Nevertheless, we have confirmed that the weak interactions of neutrinos are correctly described by the Standard Model (SM) of elementary particle physics. Moreover, in the last 14 years, we have discovered that neutrinos have nonzero masses, and that leptons mix. These discoveries have been based on the observation that neutrinos can change from one 'flavor' to another - the phenomenon known as neutrino oscillation. We shall explain the physics of neutrino oscillation, deriving the probability of oscillation in a new way. We shall also provide a very brief guide to references that can be used to study some major neutrino-physics topics other than neutrino oscillation.« less

Relation between the neutrino flux from Centaurus A and the associated diffuse neutrino flux

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koers, Hylke B. J.; Tinyakov, Peter; Institute for Nuclear Research, 60th October Anniversary Prospect 7a, 117312, Moscow

2008-10-15

Based on recent results obtained by the Pierre Auger Observatory (PAO), it has been hypothesized that Centaurus A (Cen A) is a source of ultrahigh-energy cosmic rays (UHECRs) and associated neutrinos. We point out that the diffuse neutrino flux may be used to constrain the source model if one assumes that the ratio between the UHECR and neutrino fluxes outputted by Cen A is representative for other sources. Under this assumption we investigate the relation between the neutrino flux from Cen A and the diffuse neutrino flux. Assuming furthermore that Cen A is the source of two UHECR events observedmore » by PAO, we estimate the all-sky diffuse neutrino flux to be {approx}200-5000 times larger than the neutrino flux from Cen A. As a result, the diffuse neutrino fluxes associated with some of the recently proposed models of UHECR-related neutrino production in Cen A are above existing limits. Regardless of the underlying source model, our results indicate that the detection of neutrinos from Cen A without the accompanying diffuse flux would mean that Cen A is an exceptionally efficient neutrino source.« less

Measurement of the intrinsic electron neutrino component in the T2K neutrino beam with the ND280 detector

NASA Astrophysics Data System (ADS)

Abe, K.; Adam, J.; Aihara, H.; Akiri, T.; Andreopoulos, C.; Aoki, S.; Ariga, A.; Ariga, T.; Assylbekov, S.; Autiero, D.; Barbi, M.; Barker, G. J.; Barr, G.; Bass, M.; Batkiewicz, M.; Bay, F.; Bentham, S. W.; Berardi, V.; Berger, B. E.; Berkman, S.; Bertram, I.; Bhadra, S.; Blaszczyk, F. d. M.; Blondel, A.; Bojechko, C.; Bordoni, S.; Boyd, S. B.; Brailsford, D.; Bravar, A.; Bronner, C.; Buchanan, N.; Calland, R. G.; Caravaca Rodríguez, J.; Cartwright, S. L.; Castillo, R.; Catanesi, M. G.; Cervera, A.; Cherdack, D.; Christodoulou, G.; Clifton, A.; Coleman, J.; Coleman, S. J.; Collazuol, G.; Connolly, K.; Cremonesi, L.; Dabrowska, A.; Danko, I.; Das, R.; Davis, S.; de Perio, P.; De Rosa, G.; Dealtry, T.; Dennis, S. R.; Densham, C.; Di Lodovico, F.; Di Luise, S.; Drapier, O.; Duboyski, T.; Duffy, K.; Dufour, F.; Dumarchez, J.; Dytman, S.; Dziewiecki, M.; Emery, S.; Ereditato, A.; Escudero, L.; Finch, A. J.; Floetotto, L.; Friend, M.; Fujii, Y.; Fukuda, Y.; Furmanski, A. P.; Galymov, V.; Giffin, S.; Giganti, C.; Gilje, K.; Goeldi, D.; Golan, T.; Gomez-Cadenas, J. J.; Gonin, M.; Grant, N.; Gudin, D.; Hadley, D. R.; Haesler, A.; Haigh, M. D.; Hamilton, P.; Hansen, D.; Hara, T.; Hartz, M.; Hasegawa, T.; Hastings, N. C.; Hayato, Y.; Hearty, C.; Helmer, R. L.; Hierholzer, M.; Hignight, J.; Hillairet, A.; Himmel, A.; Hiraki, T.; Hirota, S.; Holeczek, J.; Horikawa, S.; Huang, K.; Ichikawa, A. K.; Ieki, K.; Ieva, M.; Ikeda, M.; Imber, J.; Insler, J.; Irvine, T. J.; Ishida, T.; Ishii, T.; Ives, S. J.; Iwai, E.; Iyogi, K.; Izmaylov, A.; Jacob, A.; Jamieson, B.; Johnson, R. A.; Jo, J. H.; Jonsson, P.; Jung, C. K.; Kabirnezhad, M.; Kaboth, A. C.; Kajita, T.; Kakuno, H.; Kameda, J.; Kanazawa, Y.; Karlen, D.; Karpikov, I.; Kearns, E.; Khabibullin, M.; Khotjantsev, A.; Kielczewska, D.; Kikawa, T.; Kilinski, A.; Kim, J.; Kisiel, J.; Kitching, P.; Kobayashi, T.; Koch, L.; Kolaceke, A.; Konaka, A.; Kormos, L. L.; Korzenev, A.; Koseki, K.; Koshio, Y.; Kreslo, I.; Kropp, W.; Kubo, H.; Kudenko, Y.; Kumaratunga, S.; Kurjata, R.; Kutter, T.; Lagoda, J.; Laihem, K.; Lamont, I.; Larkin, E.; Laveder, M.; Lawe, M.; Lazos, M.; Lee, K. P.; Lindner, T.; Lister, C.; Litchfield, R. P.; Longhin, A.; Ludovici, L.; Macaire, M.; Magaletti, L.; Mahn, K.; Malek, M.; Manly, S.; Marino, A. D.; Marteau, J.; Martin, J. F.; Maruyama, T.; Marzec, J.; Mathie, E. L.; Matveev, V.; Mavrokoridis, K.; Mazzucato, E.; McCarthy, M.; McCauley, N.; McFarland, K. S.; McGrew, C.; Metelko, C.; Mezzetto, M.; Mijakowski, P.; Miller, C. A.; Minamino, A.; Mineev, O.; Mine, S.; Missert, A.; Miura, M.; Monfregola, L.; Moriyama, S.; Mueller, Th. A.; Murakami, A.; Murdoch, M.; Murphy, S.; Myslik, J.; Nagasaki, T.; Nakadaira, T.; Nakahata, M.; Nakai, T.; Nakamura, K.; Nakayama, S.; Nakaya, T.; Nakayoshi, K.; Naples, D.; Nielsen, C.; Nirkko, M.; Nishikawa, K.; Nishimura, Y.; O'Keeffe, H. M.; Ohta, R.; Okumura, K.; Okusawa, T.; Oryszczak, W.; Oser, S. M.; Owen, R. A.; Oyama, Y.; Palladino, V.; Palomino, J.; Paolone, V.; Payne, D.; Perevozchikov, O.; Perkin, J. D.; Petrov, Y.; Pickard, L.; Pinzon Guerra, E. S.; Pistillo, C.; Plonski, P.; Poplawska, E.; Popov, B.; Posiadala, M.; Poutissou, J.-M.; Poutissou, R.; Przewlocki, P.; Quilain, B.; Radicioni, E.; Ratoff, P. N.; Ravonel, M.; Rayner, M. A. M.; Redij, A.; Reeves, M.; Reinherz-Aronis, E.; Retiere, F.; Robert, A.; Rodrigues, P. A.; Rojas, P.; Rondio, E.; Roth, S.; Rubbia, A.; Ruterbories, D.; Sacco, R.; Sakashita, K.; Sánchez, F.; Sato, F.; Scantamburlo, E.; Scholberg, K.; Schoppmann, S.; Schwehr, J.; Scott, M.; Seiya, Y.; Sekiguchi, T.; Sekiya, H.; Sgalaberna, D.; Shiozawa, M.; Short, S.; Shustrov, Y.; Sinclair, P.; Smith, B.; Smith, R. J.; Smy, M.; Sobczyk, J. T.; Sobel, H.; Sorel, M.; Southwell, L.; Stamoulis, P.; Steinmann, J.; Still, B.; Suda, Y.; Suzuki, A.; Suzuki, K.; Suzuki, S. Y.; Suzuki, Y.; Szeglowski, T.; Tacik, R.; Tada, M.; Takahashi, S.; Takeda, A.; Takeuchi, Y.; Tanaka, H. K.; Tanaka, H. A.; Tanaka, M. M.; Terhorst, D.; Terri, R.; Thompson, L. F.; Thorley, A.; Tobayama, S.; Toki, W.; Tomura, T.; Totsuka, Y.; Touramanis, C.; Tsukamoto, T.; Tzanov, M.; Uchida, Y.; Ueno, K.; Vacheret, A.; Vagins, M.; Vasseur, G.; Wachala, T.; Waldron, A. V.; Walter, C. W.; Wark, D.; Wascko, M. O.; Weber, A.; Wendell, R.; Wilkes, R. J.; Wilking, M. J.; Wilkinson, C.; Williamson, Z.; Wilson, J. R.; Wilson, R. J.; Wongjirad, T.; Yamada, Y.; Yamamoto, K.; Yanagisawa, C.; Yen, S.; Yershov, N.; Yokoyama, M.; Yuan, T.; Yu, M.; Zalewska, A.; Zalipska, J.; Zambelli, L.; Zaremba, K.; Ziembicki, M.; Zimmerman, E. D.; Zito, M.; Żmuda, J.; T2K Collaboration

2014-05-01

The T2K experiment has reported the first observation of the appearance of electron neutrinos in a muon neutrino beam. The main and irreducible background to the appearance signal comes from the presence in the neutrino beam of a small intrinsic component of electron neutrinos originating from muon and kaon decays. In T2K, this component is expected to represent 1.2% of the total neutrino flux. A measurement of this component using the near detector (ND280), located 280 m from the target, is presented. The charged current interactions of electron neutrinos are selected by combining the particle identification capabilities of both the time projection chambers and electromagnetic calorimeters of ND280. The measured ratio between the observed electron neutrino beam component and the prediction is 1.01±0.10 providing a direct confirmation of the neutrino fluxes and neutrino cross section modeling used for T2K neutrino oscillation analyses. Electron neutrinos coming from muons and kaons decay are also separately measured, resulting in a ratio with respect to the prediction of 0.68±0.30 and 1.10±0.14, respectively.

The ELISA-measured increase in cerebrospinal fluid tau that discriminates Alzheimer's disease from other neurodegenerative disorders is not attributable to differential recognition of tau assembly forms.

PubMed

O'Dowd, Seán T; Ardah, Mustafa T; Johansson, Per; Lomakin, Aleksey; Benedek, George B; Roberts, Kinley A; Cummins, Gemma; El Agnaf, Omar M; Svensson, Johan; Zetterberg, Henrik; Lynch, Timothy; Walsh, Dominic M

2013-01-01

Elevated cerebrospinal fluid concentrations of tau discriminate Alzheimer's disease from other neurodegenerative conditions. The reasons for this are unclear. While commercial assay kits are widely used to determine total-tau concentrations, little is known about their ability to detect different aggregation states of tau. We demonstrate that the leading commercial enzyme-linked immunosorbent assay reliably detects aggregated and monomeric tau and evinces good recovery of both species when added into cerebrospinal fluid. Hence, the disparity between total-tau levels encountered in Alzheimer's disease and other neurodegenerative conditions is not due to differential recognition of tau assembly forms or the extent of degeneration.

Near-atomic model of microtubule-tau interactions.

PubMed

Kellogg, Elizabeth H; Hejab, Nisreen M A; Poepsel, Simon; Downing, Kenneth H; DiMaio, Frank; Nogales, Eva

2018-06-15

Tau is a developmentally regulated axonal protein that stabilizes and bundles microtubules (MTs). Its hyperphosphorylation is thought to cause detachment from MTs and subsequent aggregation into fibrils implicated in Alzheimer's disease. It is unclear which tau residues are crucial for tau-MT interactions, where tau binds on MTs, and how it stabilizes them. We used cryo-electron microscopy to visualize different tau constructs on MTs and computational approaches to generate atomic models of tau-tubulin interactions. The conserved tubulin-binding repeats within tau adopt similar extended structures along the crest of the protofilament, stabilizing the interface between tubulin dimers. Our structures explain the effect of phosphorylation on MT affinity and lead to a model of tau repeats binding in tandem along protofilaments, tethering together tubulin dimers and stabilizing polymerization interfaces. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

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

High-fat, high-sugar, and high-cholesterol consumption does not impact tau pathogenesis in a mouse model of Alzheimer's disease-like tau pathology.

PubMed

Gratuze, Maud; Julien, Jacinthe; Morin, Françoise; Calon, Frédéric; Hébert, Sébastien S; Marette, André; Planel, Emmanuel

2016-11-01

Aggregates of hyperphosphorylated tau protein are a pathological hallmark of Alzheimer's disease (AD). The origin of AD is multifactorial, and many metabolic disorders originating from overconsumption of fat, cholesterol, and sugar are associated with higher risk of AD later in life. However, the effects of fat, cholesterol, and sugar overconsumption on tau pathology in AD remain controversial. Using the hTau mice, a model of AD-like tau pathology, we assessed the effects of high-fat, high-cholesterol, and/or high-sugar diets on tau pathogenesis. Surprisingly, we found no effects of these compounds, even combined, on tau phosphorylation, O-GlcNAcylation, splicing, cleavage, and aggregation, suggesting that their overconsumption does not seem to worsen tau pathology in these mice. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Tau Kinetics in Neurons and the Human Central Nervous System.

PubMed

Sato, Chihiro; Barthélemy, Nicolas R; Mawuenyega, Kwasi G; Patterson, Bruce W; Gordon, Brian A; Jockel-Balsarotti, Jennifer; Sullivan, Melissa; Crisp, Matthew J; Kasten, Tom; Kirmess, Kristopher M; Kanaan, Nicholas M; Yarasheski, Kevin E; Baker-Nigh, Alaina; Benzinger, Tammie L S; Miller, Timothy M; Karch, Celeste M; Bateman, Randall J

2018-03-21

We developed stable isotope labeling and mass spectrometry approaches to measure the kinetics of multiple isoforms and fragments of tau in the human central nervous system (CNS) and in human induced pluripotent stem cell (iPSC)-derived neurons. Newly synthesized tau is truncated and released from human neurons in 3 days. Although most tau proteins have similar turnover, 4R tau isoforms and phosphorylated forms of tau exhibit faster turnover rates, suggesting unique processing of these forms that may have independent biological activities. The half-life of tau in control human iPSC-derived neurons is 6.74 ± 0.45 days and in human CNS is 23 ± 6.4 days. In cognitively normal and Alzheimer's disease participants, the production rate of tau positively correlates with the amount of amyloid plaques, indicating a biological link between amyloid plaques and tau physiology. Copyright © 2018 Elsevier Inc. All rights reserved.

Measurement of the $$\\mathrm{Z}\\gamma^{*} \\to \\tau\\tau$$ cross section in pp collisions at $$\\sqrt{s} = $$ 13 TeV and validation of $$\\tau$$ lepton analysis techniques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sirunyan, Albert M; et al.

A measurement is presented of themore » $$\\mathrm{Z}/\\gamma^{*} \\to \\tau\\tau$$ cross section in pp collisions at $$\\sqrt{s} = $$ 13 TeV, using data recorded by the CMS experiment at the LHC, corresponding to an integrated luminosity of 2.3 fb$$^{-1}$$. The product of the inclusive cross section and branching fraction is measured to be $$\\sigma(\\mathrm{pp} \\to \\mathrm{Z}/\\gamma^{*}\\text{+X}) \\, \\mathcal{B}(\\mathrm{Z}/\\gamma^{*} \\to \\tau\\tau) = $$ 1848 $$\\pm$$ 12 (stat) $$\\pm$$ 67 (syst+lumi) pb, in agreement with the standard model expectation, computed at next-to-next-to-leading order accuracy in perturbative quantum chromodynamics. The measurement is used to validate new analysis techniques relevant for future measurements of $$\\tau$$ lepton production. The measurement also provides the reconstruction efficiency and energy scale for $$\\tau$$ decays to hadrons+$$\

Behind the curtain of tauopathy: a show of multiple players orchestrating tau toxicity.

PubMed

Huang, Yunpeng; Wu, Zhihao; Zhou, Bing

2016-01-01

tau, a microtubule-associated protein, directly binds with microtubules to dynamically regulate the organization of cellular cytoskeletons, and is especially abundant in neurons of the central nervous system. Under disease conditions such as Pick's disease, progressive supranuclear palsy, frontotemporal dementia, parkinsonism linked to chromosome 17 and Alzheimer's disease, tau proteins can self-assemble to paired helical filaments progressing to neurofibrillary tangles. In these diseases, collectively referred to as "tauopathies", alterations of diverse tau modifications including phosphorylation, metal ion binding, glycosylation, as well as structural changes of tau proteins have all been observed, indicating the complexity and variability of factors in the regulation of tau toxicity. Here, we review our current knowledge and hypotheses from relevant studies on tau toxicity, emphasizing the roles of phosphorylations, metal ions, folding and clearance control underlining tau etiology and their regulations. A summary of clinical efforts and associated findings of drug candidates under development is also presented. It is hoped that a more comprehensive understanding of tau regulation will provide us with a better blueprint of tau networking in neuronal cells and offer hints for the design of more efficient strategies to tackle tau-related diseases in the future.

Oscillation characteristics of neutrino in the model with three sterile neutrinos for analysis of the anomalies on small distances

NASA Astrophysics Data System (ADS)

Khruschov, V. V.; Fomichev, S. V.

2017-11-01

In the framework of the model with three sterile neutrinos, the transition probabilities for different flavours of neutrino are calculated and the graphical dependences are obtained, in particular, for the appearance probability of electron neutrino and antineutrino in the muon neutrino and antineutrino jets as a function of distance and other model parameters at their acceptable values and at the neutrino energy less than 50 MeV, as well as a function of a ratio of distance to the neutrino energy. The theoretical results obtained can be used for analysis of the neutrino data related to the anomalies on small distances.

High-energy neutrino fluxes from AGN populations inferred from X-ray surveys

NASA Astrophysics Data System (ADS)

Jacobsen, Idunn B.; Wu, Kinwah; On, Alvina Y. L.; Saxton, Curtis J.

2015-08-01

High-energy neutrinos and photons are complementary messengers, probing violent astrophysical processes and structural evolution of the Universe. X-ray and neutrino observations jointly constrain conditions in active galactic nuclei (AGN) jets: their baryonic and leptonic contents, and particle production efficiency. Testing two standard neutrino production models for local source Cen A (Koers & Tinyakov and Becker & Biermann), we calculate the high-energy neutrino spectra of single AGN sources and derive the flux of high-energy neutrinos expected for the current epoch. Assuming that accretion determines both X-rays and particle creation, our parametric scaling relations predict neutrino yield in various AGN classes. We derive redshift-dependent number densities of each class, from Chandra and Swift/BAT X-ray luminosity functions (Silverman et al. and Ajello et al.). We integrate the neutrino spectrum expected from the cumulative history of AGN (correcting for cosmological and source effects, e.g. jet orientation and beaming). Both emission scenarios yield neutrino fluxes well above limits set by IceCube (by ˜4-106 × at 1 PeV, depending on the assumed jet models for neutrino production). This implies that: (i) Cen A might not be a typical neutrino source as commonly assumed; (ii) both neutrino production models overestimate the efficiency; (iii) neutrino luminosity scales with accretion power differently among AGN classes and hence does not follow X-ray luminosity universally; (iv) some AGN are neutrino-quiet (e.g. below a power threshold for neutrino production); (v) neutrino and X-ray emission have different duty cycles (e.g. jets alternate between baryonic and leptonic flows); or (vi) some combination of the above.

Neutrino Oscillation in a Space-Time with Torsion

NASA Astrophysics Data System (ADS)

Alimohammadi, M.; Shariati, A.

Using Einstein-Cartan-Dirac theory, we study the effect of torsion on neutrino oscillation. We see that torsion cannot induce neutrino oscillation, but affects it whenever oscillation exists for other reasons. We show that the torsion effect on neutrino oscillation is as important as the neutrino mass effect, whenever the ratio of neutrino number density to neutrino energy is ~ 1069 cm-3/eV, or the number density of the matter is ~ 1069cm-3.

Sterile Neutrinos and Seesaws

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lincoln, Don

Time and again, the study of neutrinos has confounded scientists. One very peculiar property of neutrinos is that only neutrinos with a specific spin configuration have been observed. In this video, Fermilab’s Dr. Don Lincoln talks about this and lays out the possibility that other types of neutrinos might exist, called right handed or sterile neutrinos.

Search for sterile neutrino mixing using three years of IceCube DeepCore data

NASA Astrophysics Data System (ADS)

Aartsen, M. G.; Ackermann, M.; Adams, J.; Aguilar, J. A.; Ahlers, M.; Ahrens, M.; Al Samarai, I.; Altmann, D.; Andeen, K.; Anderson, T.; Ansseau, I.; Anton, G.; Archinger, M.; Argüelles, C.; Auffenberg, J.; Axani, S.; Bai, X.; Barwick, S. W.; Baum, V.; Bay, R.; Beatty, J. J.; Becker Tjus, J.; Becker, K.-H.; BenZvi, S.; Berley, D.; Bernardini, E.; Besson, D. Z.; Binder, G.; Bindig, D.; Blaufuss, E.; Blot, S.; Bohm, C.; Börner, M.; Bos, F.; Bose, D.; Böser, S.; Botner, O.; Braun, J.; Brayeur, L.; Bretz, H.-P.; Bron, S.; Burgman, A.; Carver, T.; Casier, M.; Cheung, E.; Chirkin, D.; Christov, A.; Clark, K.; Classen, L.; Coenders, S.; Collin, G. H.; Conrad, J. M.; Cowen, D. F.; Cross, R.; Day, M.; de André, J. P. A. M.; De Clercq, C.; del Pino Rosendo, E.; Dembinski, H.; De Ridder, S.; Desiati, P.; de Vries, K. D.; de Wasseige, G.; de With, M.; DeYoung, T.; Díaz-Vélez, J. C.; di Lorenzo, V.; Dujmovic, H.; Dumm, J. P.; Dunkman, M.; Eberhardt, B.; Ehrhardt, T.; Eichmann, B.; Eller, P.; Euler, S.; Evenson, P. A.; Fahey, S.; Fazely, A. R.; Feintzeig, J.; Felde, J.; Filimonov, K.; Finley, C.; Flis, S.; Fösig, C.-C.; Franckowiak, A.; Friedman, E.; Fuchs, T.; Gaisser, T. K.; Gallagher, J.; Gerhardt, L.; Ghorbani, K.; Giang, W.; Gladstone, L.; Glauch, T.; Glüsenkamp, T.; Goldschmidt, A.; Gonzalez, J. G.; Grant, D.; Griffith, Z.; Haack, C.; Hallgren, A.; Halzen, F.; Hansen, E.; Hansmann, T.; Hanson, K.; Hebecker, D.; Heereman, D.; Helbing, K.; Hellauer, R.; Hickford, S.; Hignight, J.; Hill, G. C.; Hoffman, K. D.; Hoffmann, R.; Hoshina, K.; Huang, F.; Huber, M.; Hultqvist, K.; In, S.; Ishihara, A.; Jacobi, E.; Japaridze, G. S.; Jeong, M.; Jero, K.; Jones, B. J. P.; Kang, W.; Kappes, A.; Karg, T.; Karle, A.; Katz, U.; Kauer, M.; Keivani, A.; Kelley, J. L.; Kheirandish, A.; Kim, J.; Kim, M.; Kintscher, T.; Kiryluk, J.; Kittler, T.; Klein, S. R.; Kohnen, G.; Koirala, R.; Kolanoski, H.; Konietz, R.; Köpke, L.; Kopper, C.; Kopper, S.; Koskinen, D. J.; Kowalski, M.; Krings, K.; Kroll, M.; Krückl, G.; Krüger, C.; Kunnen, J.; Kunwar, S.; Kurahashi, N.; Kuwabara, T.; Kyriacou, A.; Labare, M.; Lanfranchi, J. L.; Larson, M. J.; Lauber, F.; Lennarz, D.; Lesiak-Bzdak, M.; Leuermann, M.; Lu, L.; Lünemann, J.; Madsen, J.; Maggi, G.; Mahn, K. B. M.; Mancina, S.; Mandelartz, M.; Maruyama, R.; Mase, K.; Maunu, R.; McNally, F.; Meagher, K.; Medici, M.; Meier, M.; Menne, T.; Merino, G.; Meures, T.; Miarecki, S.; Micallef, J.; Momenté, G.; Montaruli, T.; Moulai, M.; Nahnhauer, R.; Naumann, U.; Neer, G.; Niederhausen, H.; Nowicki, S. C.; Nygren, D. R.; Obertacke Pollmann, A.; Olivas, A.; O'Murchadha, A.; Palczewski, T.; Pandya, H.; Pankova, D. V.; Peiffer, P.; Penek, Ö.; Pepper, J. A.; Pérez de los Heros, C.; Pieloth, D.; Pinat, E.; Price, P. B.; Przybylski, G. T.; Quinnan, M.; Raab, C.; Rädel, L.; Rameez, M.; Rawlins, K.; Reimann, R.; Relethford, B.; Relich, M.; Resconi, E.; Rhode, W.; Richman, M.; Riedel, B.; Robertson, S.; Rongen, M.; Rott, C.; Ruhe, T.; Ryckbosch, D.; Rysewyk, D.; Sabbatini, L.; Sanchez Herrera, S. E.; Sandrock, A.; Sandroos, J.; Sarkar, S.; Satalecka, K.; Schlunder, P.; Schmidt, T.; Schoenen, S.; Schöneberg, S.; Schumacher, L.; Seckel, D.; Seunarine, S.; Soldin, D.; Song, M.; Spiczak, G. M.; Spiering, C.; Stachurska, J.; Stanev, T.; Stasik, A.; Stettner, J.; Steuer, A.; Stezelberger, T.; Stokstad, R. G.; Stößl, A.; Ström, R.; Strotjohann, N. L.; Sullivan, G. W.; Sutherland, M.; Taavola, H.; Taboada, I.; Tatar, J.; Tenholt, F.; Ter-Antonyan, S.; Terliuk, A.; Tešić, G.; Tilav, S.; Toale, P. A.; Tobin, M. N.; Toscano, S.; Tosi, D.; Tselengidou, M.; Tung, C. F.; Turcati, A.; Unger, E.; Usner, M.; Vandenbroucke, J.; van Eijndhoven, N.; Vanheule, S.; van Rossem, M.; van Santen, J.; Vehring, M.; Voge, M.; Vogel, E.; Vraeghe, M.; Walck, C.; Wallace, A.; Wallraff, M.; Wandkowsky, N.; Waza, A.; Weaver, Ch.; Weiss, M. J.; Wendt, C.; Westerhoff, S.; Whelan, B. J.; Wickmann, S.; Wiebe, K.; Wiebusch, C. H.; Wille, L.; Williams, D. R.; Wills, L.; Wolf, M.; Wood, T. R.; Woolsey, E.; Woschnagg, K.; Xu, D. L.; Xu, X. W.; Xu, Y.; Yanez, J. P.; Yodh, G.; Yoshida, S.; Zoll, M.; IceCube Collaboration

2017-06-01

We present a search for a light sterile neutrino using three years of atmospheric neutrino data from the DeepCore detector in the energy range of approximately 10-60 GeV. DeepCore is the low-energy subarray of the IceCube Neutrino Observatory. The standard three-neutrino paradigm can be probed by adding an additional light (Δ m412˜1 eV2 ) sterile neutrino. Sterile neutrinos do not interact through the standard weak interaction and, therefore, cannot be directly detected. However, their mixing with the three active neutrino states leaves an imprint on the standard atmospheric neutrino oscillations for energies below 100 GeV. A search for such mixing via muon neutrino disappearance is presented here. The data are found to be consistent with the standard three-neutrino hypothesis. Therefore, we derive limits on the mixing matrix elements at the level of |Uμ 4|2<0.11 and |Uτ 4|2<0.15 (90% C.L.) for the sterile neutrino mass splitting Δ m412=1.0 eV2 .

Upper bound on neutrino mass based on T2K neutrino timing measurements

NASA Astrophysics Data System (ADS)

Abe, K.; Adam, J.; Aihara, H.; Akiri, T.; Andreopoulos, C.; Aoki, S.; Ariga, A.; Assylbekov, S.; Autiero, D.; Barbi, M.; Barker, G. J.; Barr, G.; Bartet-Friburg, P.; Bass, M.; Batkiewicz, M.; Bay, F.; Berardi, V.; Berger, B. E.; Berkman, S.; Bhadra, S.; Blaszczyk, F. d. M.; Blondel, A.; Bojechko, C.; Bolognesi, S.; Bordoni, S.; Boyd, S. B.; Brailsford, D.; Bravar, A.; Bronner, C.; Buchanan, N.; Calland, R. G.; Caravaca Rodríguez, J.; Cartwright, S. L.; Castillo, R.; Catanesi, M. G.; Cervera, A.; Cherdack, D.; Chikuma, N.; Christodoulou, G.; Clifton, A.; Coleman, J.; Coleman, S. J.; Collazuol, G.; Connolly, K.; Cremonesi, L.; Dabrowska, A.; Danko, I.; Das, R.; Davis, S.; de Perio, P.; De Rosa, G.; Dealtry, T.; Dennis, S. R.; Densham, C.; Dewhurst, D.; Di Lodovico, F.; Di Luise, S.; Dolan, S.; Drapier, O.; Duboyski, T.; Duffy, K.; Dumarchez, J.; Dytman, S.; Dziewiecki, M.; Emery-Schrenk, S.; Ereditato, A.; Escudero, L.; Feusels, T.; Finch, A. J.; Fiorentini, G. A.; Friend, M.; Fujii, Y.; Fukuda, Y.; Furmanski, A. P.; Galymov, V.; Garcia, A.; Giffin, S.; Giganti, C.; Gilje, K.; Goeldi, D.; Golan, T.; Gonin, M.; Grant, N.; Gudin, D.; Hadley, D. R.; Haegel, L.; Haesler, A.; Haigh, M. D.; Hamilton, P.; Hansen, D.; Hara, T.; Hartz, M.; Hasegawa, T.; Hastings, N. C.; Hayashino, T.; Hayato, Y.; Hearty, C.; Helmer, R. L.; Hierholzer, M.; Hignight, J.; Hillairet, A.; Himmel, A.; Hiraki, T.; Hirota, S.; Holeczek, J.; Horikawa, S.; Hosomi, F.; Huang, K.; Ichikawa, A. K.; Ieki, K.; Ieva, M.; Ikeda, M.; Imber, J.; Insler, J.; Irvine, T. J.; Ishida, T.; Ishii, T.; Iwai, E.; Iwamoto, K.; Iyogi, K.; Izmaylov, A.; Jacob, A.; Jamieson, B.; Jiang, M.; Johnson, R. A.; Johnson, S.; Jo, J. H.; Jonsson, P.; Jung, C. K.; Kabirnezhad, M.; Kaboth, A. C.; Kajita, T.; Kakuno, H.; Kameda, J.; Kanazawa, Y.; Karlen, D.; Karpikov, I.; Katori, T.; Kearns, E.; Khabibullin, M.; Khotjantsev, A.; Kielczewska, D.; Kikawa, T.; Kilinski, A.; Kim, J.; King, S.; Kisiel, J.; Kitching, P.; Kobayashi, T.; Koch, L.; Koga, T.; Kolaceke, A.; Konaka, A.; Kopylov, A.; Kormos, L. L.; Korzenev, A.; Koshio, Y.; Kropp, W.; Kubo, H.; Kudenko, Y.; Kurjata, R.; Kutter, T.; Lagoda, J.; Lamont, I.; Larkin, E.; Laveder, M.; Lawe, M.; Lazos, M.; Lindner, T.; Lister, C.; Litchfield, R. P.; Longhin, A.; Lopez, J. P.; Ludovici, L.; Magaletti, L.; Mahn, K.; Malek, M.; Manly, S.; Marino, A. D.; Marteau, J.; Martin, J. F.; Martins, P.; Martynenko, S.; Maruyama, T.; Matveev, V.; Mavrokoridis, K.; Mazzucato, E.; McCarthy, M.; McCauley, N.; McFarland, K. S.; McGrew, C.; Mefodiev, A.; Metelko, C.; Mezzetto, M.; Mijakowski, P.; Miller, C. A.; Minamino, A.; Mineev, O.; Missert, A.; Miura, M.; Moriyama, S.; Mueller, Th. A.; Murakami, A.; Murdoch, M.; Murphy, S.; Myslik, J.; Nakadaira, T.; Nakahata, M.; Nakamura, K. G.; Nakamura, K.; Nakayama, S.; Nakaya, T.; Nakayoshi, K.; Nantais, C.; Nielsen, C.; Nirkko, M.; Nishikawa, K.; Nishimura, Y.; Nowak, J.; O'Keeffe, H. M.; Ohta, R.; Okumura, K.; Okusawa, T.; Oryszczak, W.; Oser, S. M.; Ovsyannikova, T.; Owen, R. A.; Oyama, Y.; Palladino, V.; Palomino, J. L.; Paolone, V.; Payne, D.; Perevozchikov, O.; Perkin, J. D.; Petrov, Y.; Pickard, L.; Pinzon Guerra, E. S.; Pistillo, C.; Plonski, P.; Poplawska, E.; Popov, B.; Posiadala-Zezula, M.; Poutissou, J.-M.; Poutissou, R.; Przewlocki, P.; Quilain, B.; Radicioni, E.; Ratoff, P. N.; Ravonel, M.; Rayner, M. A. M.; Redij, A.; Reeves, M.; Reinherz-Aronis, E.; Riccio, C.; Rodrigues, P. A.; Rojas, P.; Rondio, E.; Roth, S.; Rubbia, A.; Ruterbories, D.; Rychter, A.; Sacco, R.; Sakashita, K.; Sánchez, F.; Sato, F.; Scantamburlo, E.; Scholberg, K.; Schoppmann, S.; Schwehr, J.; Scott, M.; Seiya, Y.; Sekiguchi, T.; Sekiya, H.; Sgalaberna, D.; Shah, R.; Shaker, F.; Shaw, D.; Shiozawa, M.; Short, S.; Shustrov, Y.; Sinclair, P.; Smith, B.; Smy, M.; Sobczyk, J. T.; Sobel, H.; Sorel, M.; Southwell, L.; Stamoulis, P.; Steinmann, J.; Still, B.; Suda, Y.; Suzuki, A.; Suzuki, K.; Suzuki, S. Y.; Suzuki, Y.; Tacik, R.; Tada, M.; Takahashi, S.; Takeda, A.; Takeuchi, Y.; Tanaka, H. K.; Tanaka, H. A.; Tanaka, M. M.; Terhorst, D.; Terri, R.; Thompson, L. F.; Thorley, A.; Tobayama, S.; Toki, W.; Tomura, T.; Totsuka, Y.; Touramanis, C.; Tsukamoto, T.; Tzanov, M.; Uchida, Y.; Vacheret, A.; Vagins, M.; Vasseur, G.; Wachala, T.; Wakamatsu, K.; Walter, C. W.; Wark, D.; Warzycha, W.; Wascko, M. O.; Weber, A.; Wendell, R.; Wilkes, R. J.; Wilking, M. J.; Wilkinson, C.; Williamson, Z.; Wilson, J. R.; Wilson, R. J.; Wongjirad, T.; Yamada, Y.; Yamamoto, K.; Yanagisawa, C.; Yano, T.; Yen, S.; Yershov, N.; Yokoyama, M.; Yoo, J.; Yoshida, K.; Yuan, T.; Yu, M.; Zalewska, A.; Zalipska, J.; Zambelli, L.; Zaremba, K.; Ziembicki, M.; Zimmerman, E. D.; Zito, M.; Żmuda, J.; T2K Collaboration

2016-01-01

The Tokai to Kamioka (T2K) long-baseline neutrino experiment consists of a muon neutrino beam, produced at the J-PARC accelerator, a near detector complex and a large 295-km-distant far detector. The present work utilizes the T2K event timing measurements at the near and far detectors to study neutrino time of flight as a function of derived neutrino energy. Under the assumption of a relativistic relation between energy and time of flight, constraints on the neutrino rest mass can be derived. The sub-GeV neutrino beam in conjunction with timing precision of order tens of ns provide sensitivity to neutrino mass in the few MeV /c2 range. We study the distribution of relative arrival times of muon and electron neutrino candidate events at the T2K far detector as a function of neutrino energy. The 90% C.L. upper limit on the mixture of neutrino mass eigenstates represented in the data sample is found to be mν2<5.6 MeV2/c4 .

Implications of Fermi-LAT observations on the origin of IceCube neutrinos

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Bin; Li, Zhuo; Zhao, Xiaohong, E-mail: wang_b@pku.edu.cn, E-mail: zhaoxh@ynao.ac.cn, E-mail: zhuo.li@pku.edu.cn

2014-11-01

The IceCube (IC) collaboration recently reported the detection of TeV-PeV extraterrestrial neutrinos whose origin is yet unknown. By the photon-neutrino connection in pp and pγ interactions, we use the Fermi-LAT observations to constrain the origin of the IC detected neutrinos. We find that Galactic origins, i.e., the diffuse Galactic neutrinos due to cosmic ray (CR) propagation in the Milky Way, and the neutrinos from the Galactic point sources, may not produce the IC neutrino flux, thus these neutrinos should be of extragalactic origin. Moreover, the extragalactic gamma-ray bursts (GRBs) may not account for the IC neutrino flux, the jets ofmore » active galactic nuclei may not produce the IC neutrino spectrum, but the starburst galaxies (SBGs) may be promising sources. As suggested by the consistency between the IC detected neutrino flux and the Waxman-Bahcall bound, GRBs in SBGs may be the sources of both the ultrahigh energy, ∼> 10{sup 19}eV, CRs and the 1–100 PeV CRs that produce the IC detected TeV-PeV neutrinos.« less

Acute tau knockdown in the hippocampus of adult mice causes learning and memory deficits.

PubMed

Velazquez, Ramon; Ferreira, Eric; Tran, An; Turner, Emily C; Belfiore, Ramona; Branca, Caterina; Oddo, Salvatore

2018-05-10

Misfolded and hyperphosphorylated tau accumulates in several neurodegenerative disorders including Alzheimer's disease, frontotemporal dementia with Parkinsonism, corticobasal degeneration, progressive supranuclear palsy, Down syndrome, and Pick's disease. Tau is a microtubule-binding protein, and its role in microtubule stabilization is well defined. In contrast, while growing evidence suggests that tau is also involved in synaptic physiology, a complete assessment of tau function in the adult brain has been hampered by robust developmental compensation of other microtubule-binding proteins in tau knockout mice. To circumvent these developmental compensations and assess the role of tau in the adult brain, we generated an adeno-associated virus (AAV) expressing a doxycycline-inducible short-hairpin (Sh) RNA targeted to tau, herein referred to as AAV-ShRNATau. We performed bilateral stereotaxic injections in 7-month-old C57Bl6/SJL wild-type mice with either the AAV-ShRNATau or a control AAV. We found that acute knockdown of tau in the adult hippocampus significantly impaired motor coordination and spatial memory. Blocking the expression of the AAV-ShRNATau, thereby allowing tau levels to return to control levels, restored motor coordination and spatial memory. Mechanistically, the reduced tau levels were associated with lower BDNF levels, reduced levels of synaptic proteins associated with learning, and decreased spine density. We provide compelling evidence that tau is necessary for motor and cognitive function in the adult brain, thereby firmly supporting that tau loss-of-function may contribute to the clinical manifestations of many tauopathies. These findings have profound clinical implications given that anti-tau therapies are in clinical trials for Alzheimer's disease. © 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

No added diagnostic value of non-phosphorylated tau fraction (p-taurel) in CSF as a biomarker for differential dementia diagnosis.

PubMed

Goossens, Joery; Bjerke, Maria; Struyfs, Hanne; Niemantsverdriet, Ellis; Somers, Charisse; Van den Bossche, Tobi; Van Mossevelde, Sara; De Vil, Bart; Sieben, Anne; Martin, Jean-Jacques; Cras, Patrick; Goeman, Johan; De Deyn, Peter Paul; Van Broeckhoven, Christine; van der Zee, Julie; Engelborghs, Sebastiaan

2017-07-14

The Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers Aβ 1-42 , t-tau, and p-tau 181 overlap with other diseases. New tau modifications or epitopes, such as the non-phosphorylated tau fraction (p-tau rel ), may improve differential dementia diagnosis. The goal of this study is to investigate if p-tau rel can improve the diagnostic performance of the AD CSF biomarker panel for differential dementia diagnosis. The study population consisted of 45 AD, 45 frontotemporal lobar degeneration (FTLD), 45 dementia with Lewy bodies (DLB), and 21 Creutzfeldt-Jakob disease (CJD) patients, and 20 cognitively healthy controls. A substantial subset of the patients was pathology-confirmed. CSF levels of Aβ 1-42 , t-tau, p-tau 181 , and p-tau rel were determined with commercially available single-analyte enzyme-linked immunosorbent assay (ELISA) kits. Diagnostic performance was evaluated by receiver operating characteristic (ROC) curve analyses, and area under the curve (AUC) values were compared using DeLong tests. The diagnostic performance of single markers as well as biomarker ratios was determined for each pairwise comparison of different dementia groups and controls. The addition of p-tau rel to the AD biomarker panel decreased its diagnostic performance when discriminating non-AD, FTLD, and DLB from AD. As a single marker, p-tau rel increased the diagnostic performance for CJD. No significant difference was found in AUC values with the addition of p-tau rel when differentiating between AD or non-AD dementias and controls. The addition of p-tau rel to the AD CSF biomarker panel failed to improve differentiation between AD and non-AD dementias.

Differential effects of voluntary treadmill exercise and caloric restriction on tau pathogenesis in a mouse model of Alzheimer's disease-like tau pathology fed with Western diet.

PubMed

Gratuze, Maud; Julien, Jacinthe; Morin, Françoise; Marette, André; Planel, Emmanuel

2017-10-03

Tau is a microtubule-associated protein that becomes pathological when it undergoes hyperphosphorylation and aggregation as seen in Alzheimer's disease (AD). AD is mostly sporadic, with environmental, biological and/or genetic risks factors, interacting together to promote the disease. In the past decade, reports have suggested that obesity in midlife could be one of these risk factors. On the other hand, caloric restriction and physical exercise have been reported to reduce the incidence and outcome of obesity as well as AD. We evaluated the impact of voluntary physical exercise and caloric restriction on tau pathology during 2months in hTau mice under high caloric diet in order to evaluate if these strategies could prevent AD-like pathology in obese conditions. We found no effects of obesity induced by Western diet on both Tau phosphorylation and aggregation compared to controls. However, exercise reduced tau phosphorylation while caloric restriction exacerbated its aggregation in the brains of obese hTau mice. We then examined the mechanisms underlying changes in tau phosphorylation and aggregation by exploring major tau kinases and phosphatases and key proteins involved in autophagy. However, there were no significant effects of voluntary exercise and caloric restriction on these proteins in hTau mice that could explain our results. In this study, we report differential effects of voluntary treadmill exercise and caloric restriction on tau pathogenesis in our obese mice, namely beneficial effect of exercise on tau phosphorylation and deleterious effect of caloric restriction on tau aggregation. Our results suggest that lifestyle strategies used to reduce metabolic disorders and AD must be selected and studied carefully to avoid exacerbation of pathologies. Copyright © 2017. Published by Elsevier Inc.

Proceedings of the 29th International Conference on High Energy Physics: Ichep '98 (in 2 Volumes)

NASA Astrophysics Data System (ADS)

Astbury, Alan; Axen, David; Robinson, Jacob

1999-06-01

The Table of Contents for the book is as follows: * VOLUME I * Foreword * Conference Organization * PLENARY SESSIONS * Pl-01 Recent Results from the Super-Kamiokande * Recent Results from the Super-Kamiokande * Pl-02 Recent Results on Neutrino Oscillations * Recent Results on Neutrino Oscillations * Pl-03 Experimental Status of the Standard Model * Experimental Status of the Standard Model * Pl-04 Standard Model Theory * Standard Model Theory * Pl-05 Searches at Existing Machines * Searches at Existing Machines * Pl-06 Heavy Quark Production and Decay (t, b, and Onia) * Heavy Quark Production and Decay: (t, b, and Onia) * Pl-07 Heavy Quark Decay * Heavy Quark Decay * Pl-08 CP Violation, Rare Decays and Lepton Flavor Violation * CP Violation, Rare Decays and Lepton Flavor Violation * Pl-09 Light and Charmed Hadron Spectroscopy * Light and Charmed Hadron Spectroscopy * Pl-10 Progress in Lattice Gauge Theory * Progress in Lattice Gauge Theory * Pl-11 Structure Functions * Structure Functions * Pl-12 Diffraction and Low-Q2 Physics Including Two-Photon Physics * Diffraction and Low-Q2 Physics Including Two-Photon Physics * Pl-13 Heavy Ion Collisions at High Energy * Heavy Ion Collisions at High Energy * Pl-14 "Non-Perturbative Methods" in Field Theory * "Non-Perturbative Methods" in Field Theory * Pl-15 Experimental Aspects of QCD in e+e- Collisions * Experimental Aspects of QCD in e+e- Collisions * Pl-16 QCD at High Energy (Hadron-Hadron, Lepton-Hadron, and Gamma-Hadron) * QCD at High Energy (Hadron-Hadron, Lepton-Hadron, Gamma-Hadron) * Pl-17 Perturbative QCD Theory (Includes Our Knowledge of αs) * Perturbative QCD Theory (Includes our Knowledge of αs) * Pl-18 Experimental Particle Astrophysics * Experimental Particle Astrophysics * Pl-19 Particle Cosmology * Particle Cosmology * Pl-20 Guide to Physics Beyond the Standard Model * Guide to Physics Beyond the Standard Model * Pl-21 Developments in Superstring Theory * Developments in Superstring Theory * Pl-22 Future Accelerators * Future Accelerators * Pl-23 Summary and Outlook * Summary and Outlook * PARALLEL SESSIONS * Pa-01 Electroweak Interactions - Experiment and Theory W-boson Properties, Three Boson Couplings, LEPI/SLD Fits * Measurements of ALR and Alepton from SLD * Z Lineshape and Forward-Backward Asymmetries * New Results on the Theoretical Precision of the LEP/SLC Luminosity * Tau Polarisation Measurement at LEP * Z0 Decays to b, c-quarks * Heavy Quark Asymmetries at LEP * Fermion Pair Production at LEP2 * Two-fermion Heavy Flavour Production at LEP 2 * Single and Pair Production of Neutral Electroweak Gauge Bosons at LEP * Electroweak Radiative Corrections to W Boson Production at the Tevatron * New W and Z Results from CDF * W Boson Physics at the Tevatron * WW Cross Section and Branching Fraction Measurements at LEP * Measurement of |Vcs| in W Decays at LEP2 * Evaluation of the LEP Centre-of-mass Energy Above the W-pair Production Threshold * Measurement of the W Mass at LEP by Direct Reconstruction of W-pair Semileptonic Decays * Measurement of the W-boson Mass at LEP * W+W- Hadronic Decay Properties * Bose-Einstein Correlations in WW Events * W Boson Production at HERA * Single W Production at LEP2 * Vector Boson Pair Production and Trilinear Gauge Boson Couplings - Results from the Tevatron * Trilinear Gauge Couplings at LEP2 * Tests of Lepton Universality in τ Decays * Measurement of the Total Cross Section for the Hadronic Production by e+e- Annihilation at the Energies between 2-5 GeV * Evaluation of α(M2Z) and (g - 2)μ * E821, a New Measurement of the Muon Anomalous Magnetic Moment at B.N.L. * Measurement of sin2 θW in νN Scattering at the Tevatron * The QED Process e+e- → γγ(γ) * Electroweak Measurements, QCD and Theory Uncertainties * Combined Analysis of Precision Electroweak Results * Pa-02 Neutrino and Non Accelerator Experiments Neutrino Oscillations; Solar Neutrinos; Double Beta-decay * Atmospheric Neutrino Studies in Soudan 2 * Measurements on Atmospheric Neutrinos with O * Solutions to the Atmospheric Neutrino Problem * Solar Neutrino Measurements from Super-Kamiokande * Final Results of the Gallex Solar Neutrino Experiment * Evidence for Neutrino Oscillations at LSND * Karmen 2: A New Precision in the Search for Neutrino Oscillations * Searches for Evidence of Neutrino Mass in the NuTeV Experiment at Fermilab * New results on the νμ → ντ Oscillation Search with the CHORUS Detector * Results from the NOMAD Experiment * Neutrino Trident Production from NuTeV * Neutrino Mass: Where Do We Stand, and Where Are We Going? * The Palo Verde Neutrino Experiment * The Sudbury Neutrino Observatory * The Borexino Solar Neutrino Experiment * The HELLAZ Solar Neutrino Experiment - the Measurement of the Spectrum of νpp and νBe * Physics Opportunities with the KamLAND Experiment * Energy Spectra of Air Shower Muons as a Function of Atmospheric Depth * Radiative Four Neutrino Masses and Mixings * Pa-03 QCD, Jet Physics * Properties of Gluon and Quark Jets * QCD Tests Using bbar{b}g Events and a New Measurement of the B-Hadron Energy Distribution * Jet Structure in Deep-inelastic Scattering * Gluon Splitting Into cbar{c} and bbar{b} * Inclusive Production of Mesons and Baryons * Identified Particle Production in Quark and Gluon Jets * Multiplicity Fluctuations and Multiparticle Correlations * Fragmentation Functions and Two-Particle Correlations * Analytic QCD Flavour Thresholds Through Two Loops * NLO Calculations of the Three-jet Heavy Quark Production in e+e- - Annihilation: Status and Applications * Heavy Quark Effects and Improved Tests of the Flavour Independence of Strong Interactions * Progress in QCD Tests * Determination of Λ frac{{l( 5 right)}}{{MS}} from the Measured Energy Dependence of < 1 - Thrust > * QCD tests in Hadronic Final States * Measurements of αs from Hadronic Event Shapes in e+e- Annihilation * QCD Phase Shifts and Rising Total Cross Sections * A BFKL Monte Carlo Approach to Jet Production at Hadron-hadron and Lepton-hadron Colliders * Forward Jet and Particle Production at HERA * Jets and Prompt Photons in Photoproduction at Zeus * Inclusive Jet Production at 630 and 1800 GeV * Dijet Measurements at CDF and D0 * D*± and Inelastic J/ψ Productions at HERA * Measurement of R10 (σ(W + ≥ 1 jet)/σ(W)) at CDF * Isolated Photons without Fragmentation Contribution * Tests of Bjorken Sum Rule Using Perturbative QCD Analysis of g1(x, Q2) at Next-To-Leading Order * Pa-04 DIS, Low x; Structure Functions, Spin Structure Functions * Measurement of Neutral and Charged Current Cross Sections at High Q2 * Neutral and Charged Current DIS Cross Sections at High Q2 from ZEUS at HERA * Measurement and Phenomenology of the Proton Structure Function F2 from ZEUS at HERA * Precision Measurement of the Inclusive Deep Inelastic ep Scattering Cross Section at Low Q2 * Test of Structure Functions Using Lepton Pairs: W-Charge Asymmetry and Drell-Yan Production at CDF * Parton Distributions, d/u, and Higher Twists at High x * Determination of αs and Measurements of RL, κ, and |Vcs| from ν - N DIS at CCFR * Recent results from open charm production at H1 * Measurement of the Charm Structure Function of the Proton from D* Production and from Semileptonic Charm Decay * Comparison of Neutrino and Muon Structure Functions, Shadowing Corrections and Charge Symmetry Violation * Measurements of the Light Quark Flavor Asymmetry in the Nucleon Sea * Determination of the Flavor Asymmetry of the Light Quark Sea from Unpolarized Deep-Inelastic Scattering at HERMES * Flavor Asymmetry of the Sea Quarks in the Baryon Octet * Influence of Parton kT on High pT Particle Production and Determination of the Gluon Distribution Function * Measurements of the Spin Structure of the Nucleon from SMC experiment * Polarized Quark Distributions from Deep Inelastic Scattering * Pa-05 Low Q2, Soft Phenomena, Two Photon Physics * Next To Leading Order Parton Distributions in the Photon from γ*γ and γ*p Scattering * Photon Structure Functions at LEP * NLO Prediction for the Photoproduction of the Isolated Photon at HERA * Photon Structure * Double Diffractive J/Ψ Production in High Energy γγ Collisions and the QCD Pomeron * Charm Production in γγ Collisions at LEP * Final States in γγ and γp Interactions * The Odderon in Theory and Experiment - A Mini-Review * Leading Baryon Production in ep Scattering at HERA * Fracture Functions for Diffractive and Leading Proton DIS * Final States, Jets and Charm Production in Diffraction at HERA * Are Two Gluons the QCD Pomeron? * New Results on Diffractive Light Vector Meson Production at HERA * Heavy Vector Meson Production at HERA * Diffreactive D*s Production by Neutrinos * Observation of Self-Affine Fractality in High Energy Hadron-Hadron Collisions * VOLUME II * PARALLEL SESSIONS * Pa-06 CP Violation and Rare Decays of K, mu, and tau * Results of the Sindrum II Experiment * τ Decays to Hadrons at LEP * Spectral Functions and the Strong Coupling Constant αs in Tau Decays from OPAL * Measurement of the Tau Dipole Moments at LEP * First Search for CP Violation in Tau Lepton Decay * On A New Class of Models for Soft CP Violation * Measurement of Direct CP-Violation with the NA48 Experiment at the CERN SPS * Status of the Direct CP Violation Measurement from KTeV and Other Results * Results on CP, T, CPT Symmetries with Tagged K0 and {bar{K}^0} by CPLEAR * Investigation of CP Violation in B0 → J/ψK0S Decays at LEP with the OPAL Detector * Measurement of {B^0}/{bar{B}^0} to J/ψ K_S^0 Decay Asymmetry Using Same-Side B-Flavour Tagging * Review of Future CP-Violation Experiments in B-Meson Decays * BNL E871 Rare Kaon Decay Searches: KL → μe, KL → ee, KL → μμ * Study of K+ → π+e+e- and K+ → π+μ+μ- Decays in E865 at the AGS * KTeV at Fermilab: New K0L and π0 Rare Decay Results from Phase II of Experiment 799 * Search for Time-Reversal Violation in K+ → π0μ+ν Decay * Study of the Rare K0S, K0L, K+, K- Decays at ∫ Resonance with the CMD-2 Detector * A New Search for Direct CP Violation in Hyperon Decays * Pa-07 Production and Decay of Heavy Quarks and Onia * Update on b → sγ and b → sl+l- from CLEO * Theoretical Status of B → Xsγ Decays * b - Quark Fragmentation Measurements * Leptoproduction of J/ψ * New Results on Heavy Qbar{Q} Pair Production Close to Threshold * Properties of b-Quark Production at the Tevatron * First Observation of Open b Production at HERA * Top Quark Mass from CDF * Direct Measurement of the Top Quark Mass at DØ * Gluon Radiation in Top Mass Reconstruction: Effect of Hadronic W Decays * DØ All-Hadronic Top Decay and Top Cross Section Summary * Top Quark Production and Decay Measurements from CDF * Charge Asymmetry of Heavy Quarks at Hadron Colliders * Pa-08 Heavy Hadrons: Lifetimes: Mixing, Rare Decays * B+, B0d and b-Baryon Lifetimes * Measurements of the Bs Lifetime and Search for a Lifetime Difference frac{{ΔΓ}}{Γ } * Status of D^0 - bar{D}^0 Mixing and Doubly Cabibbo-Suppressed D0 Decay Rate Measurements * Nearby Resonances and D^0 - bar{D}^0 Mixing * Oscillations of the B0d Mesons * B0s Mixing, Limits on Δms * Semileptonic B Decays at the Z0 * Selected Results on b → cℓv from CLEO * Experimental Review on |Vub| * New Measurements of |Vub| and |Vcb| with DELPHI at LEP * A Constituent Quark-Meson Model for Heavy Meson Decays * Towards the Extraction of the CKM Angle γ * Observation of the Bc Meson at CDF * Rare Hadronic B Decays * Charmless and Double-Charm B Decays at SLD * Towards a Theory of Charmless Non-Leptonic Two-Body B Decays * Nonfactorizable Effects in Charmless B Decays and B Meson Lifetimes * B/bar{B} Flavour Tagging and Doubly Charmed B Decays in ALEPH * Production of Orbitally Excited B Mesons in Z Decays * Measurement of b-baryon Polarization in Z0 Decays * Pa-09 Light Hadron Spectroscopy (Glueballs, Exotics, States with c Quarks) * Study of D** and D*' Production in B and C Jets, with the DELPHI Detector * Recent Preliminary Results on D Meson Decays from the BES * OPAL Results on the Production of Excited Charm Mesons in Hadronic Z0 Decays * Leptonic Decays of the Ds Meson and Production of Orbitally Excited D and Ds Mesons * First Charm Hadroproduction Results from SELEX * Further Evidence on Gluonic States from the WA102 Experiment * Exotic Meson Produced in Antiproton-Neutron Annihilation: hat{p} to ηπ * Evidence for a JPC = 1-+ Exotic Mesons from BNL E852 * The 1.4 GeV JPC = 1-+ State as an Interference of a Non-Resonant Background and a Resonance at 1.6 GeV * Searches for Glueball Candidates in γγ Collisions at LEP and CESR * The Hadronic Structure in τ → 3πν Decays * Investigation of the Rare ∫ Radiative Decays with the CMD-2 Detector at VEPP-2M Collider * Radiative width of the α2 Meson * Pa-10 Searches for New Particles at Accelerators * Standard Model Higgs at LEP * Searches for Higgs Bosons Beyond the Standard Model at LEP * MSSM and Higgs Searches at the Tevatron * SUSY with Neutralino LSP at LEP * Searches for Supersymmetry at HERA * Closing the Light Gluino Window Using π+π- Pairs Produced in a Neutral Beam * Direct Search for Light Gluinos * Contact Interactions at LEP and Limits from SM Processes * Contact Interactions at HERA * Leptoquark Searches * Searches for Exotic Particles at the Tevatron * Searches for Heavy and Excited Fermions at √{s} = 183 - 189 {GeV} at LEP2 * Events with High Energy Isolated Leptons and Missing Transverse Momentum and Excited Fermion Searches at HERA * Search for Neutral Heavy Leptons in the NuTeV Experiment at Fermilab * SUSY Search with Photonic Events at LEP with tilde{G} as LSP and tilde{X}_1^0 as NLSP * Searches in Light Gravitino Scenarios with Sfermion NLSP at LEP * SUSY Searches at the Tevatron Using Photons * Search for SUSY with not{R}_p at LEP * Searches for R-Parity Violating SUSY at the Tevatron * Aspects of Higgs Physics and Physics Beyond the Standard Model at LHC and e+e- Linear Colliders * Pa-11 Particle Astrophysics (Dark Matter Searches, Extensive Air Shower, Space and Underground Experiments) * The Detection of Gravitational Waves LIGO * Status of the Gravitational Wave Detector VIRGO * Search for Rare Particles with the O Detector * A Search for Dark Matter Using Cryogenic Detectors (CDMS) * Search for P to K^{+}bar{v} with Super-Kamiokande * Status and Recent Results from the HEGRA Air Shower Experiment * TeV Gamma-Ray Astronomy at the Whipple Observatory * GLAST * Initial Results from the Amanda High Energy Neutrino Detector * ANTARES * Alpha Magnetic Spectrometer AMS Report on the First Flight in Space June 2-12 * BESS Measurement of Cosmic-Ray Antiproton Spectrum and Search for Antimatter * Pa-13 Heavy Ion Collisions at High Energies * Probing the Final and Initial State in Ultrarelativistic Heavy Ion Collisions - Results from the WA98 Experiment * Intermediate Mass Dimuons in NA38/NA50 * Results on Charmonium States in Pb-Pb Interactions * High Energy Pb+Pb Collisions as Seen by the N44 Experiment * Overview of Hadronic Observables Measured by NA49 at the CERN/SPS in Central 208Pb+Pb Collisions at 158 GeV/Nucleon * Relativistic Multiparticle Processes in the Central Rapidity Region at Asymptotically High Energies in Nuclear Collisions * Pa-14 Experimental Techniques * The Compass Experiment * Status of the BaBar Detector * The HERA-B Experiment: Overview and Concepts * The Run II Upgrade to the Collider Detector at Fermilab * The DØ Detector Upgrade and Jet Energy Scale * The KLOE Calorimetric System for Neutral Particle Detection and Triggering * Precision Luminosity Measurement with the OPAL Silicon-Tungsten Calorimeters * The ATLAS Electromagnetic Calorimeter and the ATLAS Level-1 Calorimeter Trigger * Test of CsI(Tl) Crystals for the Dark Matter Search * The Drift Chamber and the Data Acquisition System of the KLOE Experiment * Progress Towards CLEO III: The Silicon Tracker and the LiF-TEA Ring Imaging Cherenkov Detector * Status of HERA-B Sub-detectors & Operational Experience * Recent Results on the Development of Radiation-Hard Diamond Detectors * The ATLAS Transition Radiation Tracker and Recent Developments in P+N Silicon Strip Detectors for LHC * The RICH System and Vertex Detector of LHCb * Pa-15 Field Theory - Perturbative and Non Perturbative * Global Quantization of Yang-Mills Theory * Vilkovisky-DeWitt Effective Potential and the Higgs Mass Bound * Exact Results in Softly Broken SUSY Gauge Theories * Higgs Masses and s-Spectra in Finite and the Minimal SUSY Gauge-Yukawa GUT * Effective Chiral Theory of Mesons, Coefficients of ChPT, Axial Vector Symmetry Breaking * Analytic Perturbative Approach to QCD * The Perturbative QCD Potential and the tbar{t} Threshold * The Degree of Infrared Safety of Quark-Antiquark Annihilation at High Energy to All Orders * Perturbative QCD- and Power-corrected Hadron Spectra and Spectral Moments in the Decay B → Xsℓ+ℓ- * Dokshitzer-Gribov-Lipatov-Altarelli-Parisi Evolution and the Renormalization Group Improved Yennie-Frautschi-Suura Theory in QCD * Effect of Electromagnetism in Nonleptonic Kaon Decays * The Thermal Coupling Constant in the Vector λφ4D Model * Fixed Point Structure of Padé-Summation Approximations to the QCD β-Function * Problem of Divergent Energy-integrals in the Coulomb Gauge * Nonlocal Color Interactions in a Gauge-Invariant Formulation of QCD * On Scalar Field Theories with Polynomial Interactions * Pa-16 Beyond the Standard Model - Theory * The Fermion Mass Problem and the Anti-Grand Unification Model * Grand Unification from Gauge Theory in M4 × ZN * SU(N) SUSY GUTs with String Remnants: Minimal SU(5) and Beyond * The Dualized Standard Model and Its Applications * Predictions for SUSY Particle Masses from Electroweak Baryogenesis * Selected Low-Energy Supersymmetry Phenomenology Topics * Tau Leptons as the New Signal for Supersymmetry * Resonant Slepton Production at Hadron Colliders in R-Parity Violating Models * Extracting Chargino/Neutralino Mass Parameters from Physical Observables * Radiative Corrections in the MSSM Beyond One-Loop: Precision Observables and Neutral Higgs Masses * Bosonic Decays of tilde{t}_2 and tilde{b}_2 Including SUSY-QCD Corrections * Discovery Limits for Techni-Omega Production in eγ Collisions * Majorana Neutrino Transition Magnetic Moments in L-Right Symmetric Models * Light Rays of New Physics: CP Violation in B → Xsγ Decays * Lessons from bar{B} to X_{S}γ in Two Higgs Doublet Models * Scalar-Mediated Flavor-Changing Neutral Currents * Anomalous Higgs Couplings at Colliders * Pa-17 Superstrings * Stable Non-BPS States in String Theory * Duality in String Cosmology * Zero Temperature Phase Transitions in Gauge Theories * Newtonian Dynamics in an Infinite Momentum Frame * Non-perturbative Results in Global SUSY and Topological Field Theories * Supergravity Predictions for Dark Matter * Pa-18 Lattice Gauge Theory * Chirality on the Lattice * Gauge Invariant Properties of Abelian Monopoles * Theoretical Aspects of Topologically Unquenched QCD * Quantum Hall Dynamics on von Neumann Lattice * Toward the Chiral Limit of QCD: Quenched and Dynamical Domain Wall Fermions * Gauge Invariant Field Strength Correlators in QCD * Gauge Fixing on the Lattice and the Gibbs Phenomenon * Improved Lattice Actions and Charmed Hadrons * List of Participants * Conference Photos

Long-Baseline Neutrino Facility (LBNF) and Deep Underground Neutrino Experiment (DUNE): Conceptual Design Report. Volume 1: The LBNF and DUNE Projects

DOE Office of Scientific and Technical Information (OSTI.GOV)

Acciarri, R.

2016-01-22

This document presents the Conceptual Design Report (CDR) put forward by an international neutrino community to pursue the Deep Underground Neutrino Experiment at the Long-Baseline Neutrino Facility (LBNF/DUNE), a groundbreaking science experiment for long-baseline neutrino oscillation studies and for neutrino astrophysics and nucleon decay searches. The DUNE far detector will be a very large modular liquid argon time-projection chamber (LArTPC) located deep underground, coupled to the LBNF multi-megawatt wide-band neutrino beam. DUNE will also have a high-resolution and high-precision near detector.

Exploring a nonminimal sterile neutrino model involving decay at IceCube

NASA Astrophysics Data System (ADS)

Moss, Z.; Moulai, M. H.; Argüelles, C. A.; Conrad, J. M.

2018-03-01

We study the phenomenology of neutrino decay together with neutrino oscillations in the context of eV-scale sterile neutrinos. We review the formalism of visible neutrino decay in which one of the decay products is a neutrino that potentially can be observed. We apply the formalism developed for decay to the recent sterile neutrino search performed by IceCube with TeV neutrinos. We show that for a ν4 lifetime τ4/m4≲10-16 eV-1 s , the interpretation of the high-energy IceCube analysis can be significantly changed.

Resonant Production of Sterile Neutrinos in the Early Universe

NASA Astrophysics Data System (ADS)

Gilbert, Lauren; Grohs, Evan; Fuller, George M.

2016-06-01

This study examines the cosmological impacts of a light resonantly produced sterile neutrino in the early universe. Such a neutrino could be produced through lepton number-driven Mikheyev-Smirnov-Wolfenstein (MSW) conversion of active neutrinos around big bang nucleosynthesis (BBN), resulting in a non-thermal spectrum of both sterile and electron neutrinos. During BBN, the neutron-proton ratio depends sensitively on the electron neutrino flux. If electron neutrinos are being converted to sterile neutrinos, this makes the n/p ratio a probe of possible new physics. We use observations of primordial Yp and D/H to place limits on this process.

Phosphorylated human tau associates with mouse prion protein amyloid in scrapie-infected mice but does not increase progression of clinical disease.

PubMed

Race, Brent; Phillips, Katie; Kraus, Allison; Chesebro, Bruce

2016-07-03

Tauopathies are a family of neurodegenerative diseases in which fibrils of human hyperphosphorylated tau (P-tau) are believed to cause neuropathology. In Alzheimer disease, P-tau associates with A-beta amyloid and contributes to disease pathogenesis. In familial human prion diseases and variant CJD, P-tau often co-associates with prion protein amyloid, and might also accelerate disease progression. To test this latter possibility, here we compared progression of amyloid prion disease in vivo after scrapie infection of mice with and without expression of human tau. The mice used expressed both anchorless prion protein (PrP) and membrane-anchored PrP, that generate disease associated amyloid and non-amyloid PrP (PrPSc) after scrapie infection. Human P-tau induced by scrapie infection was only rarely associated with non-amyloid PrPSc, but abundant human P-tau was detected at extracellular, perivascular and axonal deposits associated with amyloid PrPSc. This pathology was quite similar to that seen in familial prion diseases. However, association of human and mouse P-tau with amyloid PrPSc did not diminish survival time following prion infection in these mice. By analogy, human P-tau may not affect prion disease progression in humans. Alternatively, these results might be due to other factors, including rapidity of disease, blocking effects by mouse tau, or low toxicity of human P-tau in this model.

Extending the Search for Muon Neutrinos Coincident with Gamma-Ray Bursts in IceCube Data

NASA Astrophysics Data System (ADS)

Aartsen, M. G.; Ackermann, M.; Adams, J.; Aguilar, J. A.; Ahlers, M.; Ahrens, M.; Samarai, I. Al; Altmann, D.; Andeen, K.; Anderson, T.; Ansseau, I.; Anton, G.; Archinger, M.; Argüelles, C.; Auffenberg, J.; Axani, S.; Bai, X.; Barwick, S. W.; Baum, V.; Bay, R.; Beatty, J. J.; Becker Tjus, J.; Becker, K.-H.; BenZvi, S.; Berley, D.; Bernardini, E.; Besson, D. Z.; Binder, G.; Bindig, D.; Blaufuss, E.; Blot, S.; Bohm, C.; Börner, M.; Bos, F.; Bose, D.; Böser, S.; Botner, O.; Braun, J.; Brayeur, L.; Bretz, H.-P.; Bron, S.; Burgman, A.; Carver, T.; Casier, M.; Cheung, E.; Chirkin, D.; Christov, A.; Clark, K.; Classen, L.; Coenders, S.; Collin, G. H.; Conrad, J. M.; Cowen, D. F.; Cross, R.; Day, M.; de André, J. P. A. M.; De Clercq, C.; del Pino Rosendo, E.; Dembinski, H.; De Ridder, S.; Desiati, P.; de Vries, K. D.; de Wasseige, G.; de With, M.; DeYoung, T.; Díaz-Vélez, J. C.; di Lorenzo, V.; Dujmovic, H.; Dumm, J. P.; Dunkman, M.; Eberhardt, B.; Ehrhardt, T.; Eichmann, B.; Eller, P.; Euler, S.; Evenson, P. A.; Fahey, S.; Fazely, A. R.; Feintzeig, J.; Felde, J.; Filimonov, K.; Finley, C.; Flis, S.; Fösig, C.-C.; Franckowiak, A.; Friedman, E.; Fuchs, T.; Gaisser, T. K.; Gallagher, J.; Gerhardt, L.; Ghorbani, K.; Giang, W.; Gladstone, L.; Glauch, T.; Glüsenkamp, T.; Goldschmidt, A.; Gonzalez, J. G.; Grant, D.; Griffith, Z.; Haack, C.; Hallgren, A.; Halzen, F.; Hansen, E.; Hansmann, T.; Hanson, K.; Hebecker, D.; Heereman, D.; Helbing, K.; Hellauer, R.; Hickford, S.; Hignight, J.; Hill, G. C.; Hoffman, K. D.; Hoffmann, R.; Hoshina, K.; Huang, F.; Huber, M.; Hultqvist, K.; In, S.; Ishihara, A.; Jacobi, E.; Japaridze, G. S.; Jeong, M.; Jero, K.; Jones, B. J. P.; Kang, W.; Kappes, A.; Karg, T.; Karle, A.; Katz, U.; Kauer, M.; Keivani, A.; Kelley, J. L.; Kheirandish, A.; Kim, J.; Kim, M.; Kintscher, T.; Kiryluk, J.; Kittler, T.; Klein, S. R.; Kohnen, G.; Koirala, R.; Kolanoski, H.; Konietz, R.; Köpke, L.; Kopper, C.; Kopper, S.; Koskinen, D. J.; Kowalski, M.; Krings, K.; Kroll, M.; Krückl, G.; Krüger, C.; Kunnen, J.; Kunwar, S.; Kurahashi, N.; Kuwabara, T.; Kyriacou, A.; Labare, M.; Lanfranchi, J. L.; Larson, M. J.; Lauber, F.; Lennarz, D.; Lesiak-Bzdak, M.; Leuermann, M.; Lu, L.; Lünemann, J.; Madsen, J.; Maggi, G.; Mahn, K. B. M.; Mancina, S.; Mandelartz, M.; Maruyama, R.; Mase, K.; Maunu, R.; McNally, F.; Meagher, K.; Medici, M.; Meier, M.; Menne, T.; Merino, G.; Meures, T.; Miarecki, S.; Micallef, J.; Momenté, G.; Montaruli, T.; Moulai, M.; Nahnhauer, R.; Naumann, U.; Neer, G.; Niederhausen, H.; Nowicki, S. C.; Nygren, D. R.; Obertacke Pollmann, A.; Olivas, A.; O'Murchadha, A.; Palczewski, T.; Pandya, H.; Pankova, D. V.; Peiffer, P.; Penek, Ö.; Pepper, J. A.; Pérez de los Heros, C.; Pieloth, D.; Pinat, E.; Price, P. B.; Przybylski, G. T.; Quinnan, M.; Raab, C.; Rädel, L.; Rameez, M.; Rawlins, K.; Reimann, R.; Relethford, B.; Relich, M.; Resconi, E.; Rhode, W.; Richman, M.; Riedel, B.; Robertson, S.; Rongen, M.; Rott, C.; Ruhe, T.; Ryckbosch, D.; Rysewyk, D.; Sabbatini, L.; Sanchez Herrera, S. E.; Sandrock, A.; Sandroos, J.; Sarkar, S.; Satalecka, K.; Schlunder, P.; Schmidt, T.; Schoenen, S.; Schöneberg, S.; Schumacher, L.; Seckel, D.; Seunarine, S.; Soldin, D.; Song, M.; Spiczak, G. M.; Spiering, C.; Stachurska, J.; Stanev, T.; Stasik, A.; Stettner, J.; Steuer, A.; Stezelberger, T.; Stokstad, R. G.; Stößl, A.; Ström, R.; Strotjohann, N. L.; Sullivan, G. W.; Sutherland, M.; Taavola, H.; Taboada, I.; Tatar, J.; Tenholt, F.; Ter-Antonyan, S.; Terliuk, A.; Tešić, G.; Tilav, S.; Toale, P. A.; Tobin, M. N.; Toscano, S.; Tosi, D.; Tselengidou, M.; Tung, C. F.; Turcati, A.; Unger, E.; Usner, M.; Vandenbroucke, J.; van Eijndhoven, N.; Vanheule, S.; van Rossem, M.; van Santen, J.; Vehring, M.; Voge, M.; Vogel, E.; Vraeghe, M.; Walck, C.; Wallace, A.; Wallraff, M.; Wandkowsky, N.; Waza, A.; Weaver, Ch.; Weiss, M. J.; Wendt, C.; Westerhoff, S.; Whelan, B. J.; Wickmann, S.; Wiebe, K.; Wiebusch, C. H.; Wille, L.; Williams, D. R.; Wills, L.; Wolf, M.; Wood, T. R.; Woolsey, E.; Woschnagg, K.; Xu, D. L.; Xu, X. W.; Xu, Y.; Yanez, J. P.; Yodh, G.; Yoshida, S.; Zoll, M.; IceCube Collaboration

2017-07-01

We present an all-sky search for muon neutrinos produced during the prompt γ-ray emission of 1172 gamma-ray bursts (GRBs) with the IceCube Neutrino Observatory. The detection of these neutrinos would constitute evidence for ultra-high-energy cosmic-ray (UHECR) production in GRBs, as interactions between accelerated protons and the prompt γ-ray field would yield charged pions, which decay to neutrinos. A previously reported search for muon neutrino tracks from northern hemisphere GRBs has been extended to include three additional years of IceCube data. A search for such tracks from southern hemisphere GRBs in five years of IceCube data has been introduced to enhance our sensitivity to the highest energy neutrinos. No significant correlation between neutrino events and observed GRBs is seen in the new data. Combining this result with previous muon neutrino track searches and a search for cascade signature events from all neutrino flavors, we obtain new constraints for single-zone fireball models of GRB neutrino and UHECR production.

Nuclear Neutrino Spectra in Late Stellar Evolution

NASA Astrophysics Data System (ADS)

Misch, G. Wendell; Sun, Yang; Fuller, George

2018-05-01

Neutrinos are the principle carriers of energy in massive stars, beginning from core carbon burning and continuing through core collapse and after the core bounce. In fact, it may be possible to detect neutrinos from nearby pre-supernova stars. Therefore, it is of great interest to understand the neutrino energy spectra from these stars. Leading up to core collapse, beginning around core silicon burning, nuclei become dominant producers of neutrinos, particularly at high neutrino energy, so a systematic study of nuclear neutrino spectra is desirable. We have done such a study, and we present our sd-shell model calculations of nuclear neutrino energy spectra for nuclei in the mass number range A = 21 - 35. Our study includes neutrinos produced by charged lepton capture, charged lepton emission, and neutral current nuclear deexcitation. Previous authors have tabulated the rates of charged current nuclear weak interactions in astrophysical conditions, but the present work expands on this not only by providing neutrino energy spectra, but also by including the heretofore untabulated neutral current de-excitation neutrino pairs.

A Simple Method to Avoid Nonspecific Signal When Using Monoclonal Anti-Tau Antibodies in Western Blotting of Mouse Brain Proteins.

PubMed

Petry, Franck R; Nicholls, Samantha B; Hébert, Sébastien S; Planel, Emmanuel

2017-01-01

In Alzheimer's disease and other tauopathies, tau displays several abnormal post-translation modifications such as hyperphosphorylation, truncation, conformation, and oligomerization. Mouse monoclonal antibodies have been raised against such tau modifications for research, diagnostic, and therapeutic purposes. However, many of these primary antibodies are at risk of giving nonspecific signals in common Western blotting procedures. Not because they are unspecific, but because the secondary antibodies used to detect them will also detect the heavy chain of endogenous mouse immunoglobulins (Igs), and give a nonspecific signal at the same molecular weight than tau protein (around 50 kDa). Here, we propose the use of anti-light chain secondary antibodies as a simple and efficient technique to prevent nonspecific Igs signals at around 50 kDa. We demonstrate the efficacy of this method by removing artifactual signals when using monoclonal antibodies directed at tau phosphorylation (AT100, 12E8, AT270), tau truncation (TauC3), tau oligomerization (TOMA), or tau abnormal conformation (Alz50), in wild-type, 3×Tg-AD, and tau knockout mice.

Dexmedetomidine Increases Tau Phosphorylation Under Normothermic Conditions In Vivo and In Vitro

PubMed Central

Whittington, Robert A.; Virág, László; Gratuze, Maud; Petry, Franck R.; Noël, Anastasia; Poitras, Isabelle; Truchetti, Geoffrey; Marcouiller, François; Papon, Marie-Amélie; Khoury, Noura El; Wong, Kevin; Bretteville, Alexis; Morin, Françoise; Planel, Emmanuel

2015-01-01

There is developing interest in the potential association between anesthesia and the onset and progression of Alzheimer's disease. Several anesthetics have thus been demonstrated to induce tau hyperphosphorylation, an effect mostly mediated by anesthesia-induced hypothermia. Here, we tested the hypothesis that acute normothermic administration of dexmedetomidine, an intravenous sedative used in intensive care units, would result in tau hyperphosphorylation in vivo and in vitro. When administered to non-transgenic mice, dexmedetomidine induced tau hyperphosphorylation persisting up to 6h in the hippocampus for the AT8 epitope. Pretreatment with atipamezole, a highly specific α2-adrenergic receptor (α2-AR) antagonist, blocked dexmedetomidine-induced tau hyperphosphorylation. Furthermore, dexmedetomidine dose-dependently increased tau phosphorylation at AT8 in SH-SY5Y cells, impaired mice spatial memory in the Barnes maze, and promoted tau hyperphosphorylation and aggregation in transgenic hTau mice. These findings suggest that dexmedetomidine: i) increases tau phosphorylation, in vivo and in vitro, in the absence of anesthetic-induced hypothermia and through α2-AR activation, ii) promotes tau aggregation in a mouse model of tauopathy, and iii) impacts spatial reference memory. PMID:26058840

Association of Cerebrospinal Fluid β-Amyloid 1-42, T-tau, P-tau181, and α-Synuclein Levels With Clinical Features of Drug-Naive Patients With Early Parkinson Disease

PubMed Central

Kang, Ju-Hee; Irwin, David J.; Chen-Plotkin, Alice S.; Siderowf, Andrew; Caspell, Chelsea; Coffey, Christopher S.; Waligórska, Teresa; Taylor, Peggy; Pan, Sarah; Frasier, Mark; Marek, Kenneth; Kieburtz, Karl; Jennings, Danna; Simuni, Tanya; Tanner, Caroline M.; Singleton, Andrew; Toga, Arthur W.; Chowdhury, Sohini; Mollenhauer, Brit; Trojanowski, John Q.; Shaw, Leslie M.

2014-01-01

Importance We observed a significant correlation between cerebrospinal fluid (CSF) levels of tau proteins and α-synuclein, but not β-amyloid 1–42 (Aβ1–42), and lower concentration of CSF biomarkers, as compared with healthy controls, in a cohort of entirely untreated patients with Parkinson disease (PD) at the earliest stage of the disease studied so far. Objective To evaluate the baseline characteristics and relationship to clinical features of CSF biomarkers (Aβ1–42, total tau [T-tau], tau phosphorylated at threonine 181 [P-tau181], and α-synuclein) in drug-naive patients with early PD and demographically matched healthy controls enrolled in the Parkinson’s Progression Markers Initiative (PPMI) study. Design, Setting, and Participants Cross-sectional study of the initial 102 research volunteers (63 patients with PD and 39 healthy controls) of the PPMI cohort. Main Outcomes and Measures The CSF biomarkers were measured by INNO-BIA AlzBio3 immunoassay (Aβ1–42, T-tau, and P-tau181; Innogenetics Inc) or by enzyme-linked immunosorbent assay (α-synuclein). Clinical features including diagnosis, demographic characteristics, motor, neuropsychiatric, and cognitive assessments, and DaTscan were systematically assessed according to the PPMI study protocol. Results Slightly, but significantly, lower levels of Aβ1–42, T-tau, P-tau181, α-synuclein, and T-tau/Aβ1–42 were seen in subjects with PD compared with healthy controls but with a marked overlap between groups. Using multivariate regression analysis, we found that lower Aβ1–42 and P-tau181 levels were associated with PD diagnosis and that decreased CSF T-tau and α-synuclein were associated with increased motor severity. Notably, when we classified patients with PD by their motor phenotypes, lower CSF Aβ1–42 and P-tau181 concentrations were associated with the postural instability–gait disturbance–dominant phenotype but not with the tremor-dominant or intermediate phenotype. Finally, we found a significant correlation of the levels of α-synuclein with the levels of T-tau and P-tau181. Conclusions and Relevance In this first report of CSF biomarkers in PPMI study subjects, we found that measures of CSF Aβ1–42, T-tau, P-tau181, and α-synuclein have prognostic and diagnostic potential in early-stage PD. Further investigations using the entire PPMI cohort will test the predictive performance of CSF biomarkers for PD progression. PMID:23979011

From Atmospheric Neutrinos to the Neutrino Mass Hierarchy

NASA Astrophysics Data System (ADS)

Kappes, A.

2015-08-01

After a brief introduction to neutrino oscillation, the article discusses how proposed detectors like PINGU and ORCA can use atmospheric neutrinos in the GeV range to determine the neutrino mass hierarchy, one of the crucial unknowns in the neutrino sector of particle physics, and what uncertainties on external input parameters have to be taken into account.

Comparison of multiple tau-PET measures as biomarkers in aging and Alzheimer's disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maass, Anne; Landau, Susan; Baker, Suzanne L.

The recent development of tau-specific positron emission tomography (PET) tracers enables in vivo quantification of regional tau pathology, one of the key lesions in Alzheimer's disease (AD). Tau PET imaging may become a useful biomarker for clinical diagnosis and tracking of disease progression but there is no consensus yet on how tau PET signal is best quantified. The goal of the current paper was to evaluate multiple whole-brain and region-specific approaches to detect clinically relevant tau PET signal. Two independent cohorts of cognitively normal adults and amyloid-positive (Aβ +) patients with mild cognitive impairment (MCI) or AD-dementia underwent [ 18F]AV-1451more » PET. Methods for tau tracer quantification included: (i) in vivo Braak staging, (ii) regional uptake in Braak composite regions, (iii) several whole-brain measures of tracer uptake, (iv) regional uptake in AD-vulnerable voxels, and (v) uptake in a priori defined regions. Receiver operating curves characterized accuracy in distinguishing Aβ - controls from AD/MCI patients and yielded tau positivity cutoffs. Clinical relevance of tau PET measures was assessed by regressions against cognition and MR imaging measures. Key tracer uptake patterns were identified by a factor analysis and voxel-wise contrasts. Braak staging, global and region-specific tau measures yielded similar diagnostic accuracies, which differed between cohorts. While all tau measures were related to amyloid and global cognition, memory and hippocampal/entorhinal volume/thickness were associated with regional tracer retention in the medial temporal lobe. Key regions of tau accumulation included medial temporal and inferior/middle temporal regions, retrosplenial cortex, and banks of the superior temporal sulcus. Finally, our data indicate that whole-brain tau PET measures might be adequate biomarkers to detect AD-related tau pathology. However, regional measures covering AD-vulnerable regions may increase sensitivity to early tau PET signal, atrophy and memory decline.« less

Looking for Sterile Neutrinos via Neutral-Current Disappearance with NOvA

NASA Astrophysics Data System (ADS)

Yang, Shaokai; NOvA Collaboration

2017-01-01

Contradictory evidence has been presented on the issue of neutrino mixing between the three known active neutrinos and light sterile neutrinos. The excess of events as seen by the LSND and MiniBooNE experiments interpreted as short-baseline neutrino oscillations, the collective evidence of the reactor neutrino anomaly, and the gallium anomaly all point towards sterile neutrinos with mass at the 1 eV level. While these results are tantalizing, they are not conclusive as they are in tension with null results from other short-baseline experiments, and with disappearance searches in long-baseline and atmospheric experiments. Resolving the issue of the existence of light sterile neutrinos has profound implications for both particle physics and cosmology. The NOvA (NuMI Off-Axis νe Appearance) experiment may help clarify the situation by searching for disappearance of active neutrinos from the NuMI (Neutrinos from the Main Injector) beam over a baseline of 810 km. In this talk, we will describe a method of how NOvA can look for oscillations into sterile neutrinos, with focus on disappearance of neutral current (NC) neutrino events, will present the first analysis result of this search, discuss their implications in constraining the existence of light sterile neutrinos, and the planned updates to this analysis.

Molecular mechanism of tau aggregation induced by anionic and cationic dyes.

PubMed

Lira-De León, Karla I; García-Gutiérrez, Ponciano; Serratos, Iris N; Palomera-Cárdenas, Marianela; Figueroa-Corona, María Del P; Campos-Peña, Victoria; Meraz-Ríos, Marco A

2013-01-01

Abnormal tau filaments are a hallmark of Alzheimer's disease. Anionic dyes such as Congo Red, Thiazine Red, and Thioflavin S are able to induce tau fibrillization in vitro. SH-SY5Y cells were incubated with each dye for seven days leading to intracellular aggregates of tau protein, with different morphological characteristics. Interestingly, these tau aggregates were not observed when the Methylene Blue dye was added to the cell culture. In order to investigate the molecular mechanisms underlying this phenomenon, we developed a computational model for the interaction of the tau paired helical filament (PHF) core with every dye by docking analysis. The polar/electrostatic and nonpolar contribution to the free binding energy in the tau PHF core-anionic dye interaction was determined. We found that the tau PHF core can generate a positive net charge within the binding site localized at residuesLys311 and Lys340 (numbering according to the longest isoform hTau40). These residues are important for the binding affinity of the negative charges present in the anionic dyes causing an electrostatic environment that stabilizes the complex. Tau PHF core protofibril-Congo Red interaction has a stronger binding affinity compared to Thiazine Red or Thioflavin S. By contrast, the cationic dye Methylene Blue does not bind to nor stabilize the tau PHF core protofibrils. These results characterize the driving forces responsible for the binding of tau to anionic dyes leading to their self-aggregation and suggest that Methylene Blue may act as a destabilizing agent of tau aggregates.

Acetylated tau destabilizes the cytoskeleton in the axon initial segment and is mislocalized to the somatodendritic compartment.

PubMed

Sohn, Peter Dongmin; Tracy, Tara E; Son, Hye-In; Zhou, Yungui; Leite, Renata E P; Miller, Bruce L; Seeley, William W; Grinberg, Lea T; Gan, Li

2016-06-29

Neurons are highly polarized cells in which asymmetric axonal-dendritic distribution of proteins is crucial for neuronal function. Loss of polarized distribution of the axonal protein tau is an early sign of Alzheimer's disease (AD) and other neurodegenerative disorders. The cytoskeletal network in the axon initial segment (AIS) forms a barrier between the axon and the somatodentritic compartment, contributing to axonal retention of tau. Although perturbation of the AIS cytoskeleton has been implicated in neurological disorders, the molecular triggers and functional consequence of AIS perturbation are incompletely understood. Here we report that tau acetylation and consequent destabilization of the AIS cytoskeleton promote the somatodendritic mislocalization of tau. AIS cytoskeletal proteins, including ankyrin G and βIV-spectrin, were downregulated in AD brains and negatively correlated with an increase in tau acetylated at K274 and K281. AIS proteins were also diminished in transgenic mice expressing tauK274/281Q, a tau mutant that mimics K274 and K281 acetylation. In primary neuronal cultures, the tauK274/281Q mutant caused hyperdynamic microtubules (MTs) in the AIS, shown by live-imaging of MT mobility and fluorescence recovery after photobleaching. Using photoconvertible tau constructs, we found that axonal tauK274/281Q was missorted into the somatodendritic compartment. Stabilizing MTs with epothilone D to restore the cytoskeletal barrier in the AIS prevented tau mislocalization in primary neuronal cultures. Together, these findings demonstrate that tau acetylation contributes to the pathogenesis of neurodegenerative disease by compromising the cytoskeletal sorting machinery in the AIS.

The L266V tau mutation is associated with frontotemporal dementia and Pick-like 3R and 4R tauopathy.

PubMed

Hogg, Marion; Grujic, Zoran M; Baker, Matt; Demirci, Serpil; Guillozet, Angela L; Sweet, Alison P; Herzog, Laura L; Weintraub, Sandra; Mesulam, M-Marsel; LaPointe, Nichole E; Gamblin, T C; Berry, Robert W; Binder, Lester I; de Silva, Rohan; Lees, Andrew; Espinoza, Marisol; Davies, Peter; Grover, Andrew; Sahara, Naruhiko; Ishizawa, Takashi; Dickson, Dennis; Yen, Shu-Hui; Hutton, Michael; Bigio, Eileen H

2003-10-01

We report a case of rapidly progressive frontotemporal dementia presenting at age 33 years. At autopsy there was severe atrophy of the frontal and temporal lobes. Tau-positive Pick bodies, which ultrastructurally were composed of straight filaments, were present, accompanied by severe neuronal loss and gliosis. RD3, a tau antibody specific for the three-repeat (3R) isoforms, labeled the Pick bodies. ET3, a four-repeat (4R) isoform-specific tau antibody, did not label Pick bodies, but highlighted rare astrocytes, and threads in white matter bundles in the corpus striatum. Analysis of the tau gene revealed an L266V mutation in exon 9. Analysis of brain tissue from this case revealed elevated levels of exon 10+ tau RNA and soluble 4R tau. However, both 3R and 4R isoforms were present in sarkosyl-insoluble tau fractions with a predominance of the shortest 3R isoform. The L266V mutation is associated with decreased rate and extent of tau-induced microtubule assembly, and a 3R isoform-specific increase in tau self assembly as measured by an in vitro assay. Combined, these data indicate that L266V is a pathogenic tau mutation that is associated with Pick-like pathology. In addition, the results of the RD3 and ET3 immunostains clearly explain for the first time the presence of both 3R and 4R tau isoforms in preparations of insoluble tau from some Pick's disease cases.

Tau-Induced Ca2+/Calmodulin-Dependent Protein Kinase-IV Activation Aggravates Nuclear Tau Hyperphosphorylation.

PubMed

Wei, Yu-Ping; Ye, Jin-Wang; Wang, Xiong; Zhu, Li-Ping; Hu, Qing-Hua; Wang, Qun; Ke, Dan; Tian, Qing; Wang, Jian-Zhi

2018-04-01

Hyperphosphorylated tau is the major protein component of neurofibrillary tangles in the brains of patients with Alzheimer's disease (AD). However, the mechanism underlying tau hyperphosphorylation is not fully understood. Here, we demonstrated that exogenously expressed wild-type human tau40 was detectable in the phosphorylated form at multiple AD-associated sites in cytoplasmic and nuclear fractions from HEK293 cells. Among these sites, tau phosphorylated at Thr205 and Ser214 was almost exclusively found in the nuclear fraction at the conditions used in the present study. With the intracellular tau accumulation, the Ca 2+ concentration was significantly increased in both cytoplasmic and nuclear fractions. Further studies using site-specific mutagenesis and pharmacological treatment demonstrated that phosphorylation of tau at Thr205 increased nuclear Ca 2+ concentration with a simultaneous increase in the phosphorylation of Ca 2+ /calmodulin-dependent protein kinase IV (CaMKIV) at Ser196. On the other hand, phosphorylation of tau at Ser214 did not significantly change the nuclear Ca 2+ /CaMKIV signaling. Finally, expressing calmodulin-binding protein-4 that disrupts formation of the Ca 2+ /calmodulin complex abolished the okadaic acid-induced tau hyperphosphorylation in the nuclear fraction. We conclude that the intracellular accumulation of phosphorylated tau, as detected in the brains of AD patients, can trigger nuclear Ca 2+ /CaMKIV signaling, which in turn aggravates tau hyperphosphorylation. Our findings provide new insights for tauopathies: hyperphosphorylation of intracellular tau and an increased Ca 2+ concentration may induce a self-perpetuating harmful loop to promote neurodegeneration.

Possible explanation of the solar-neutrino puzzle

NASA Technical Reports Server (NTRS)

Bethe, H. A.

1986-01-01

A new derivation of the Mikheyev and Smirnov (1985) mechanism for the conversion of electron neutrinos into mu neutrinos when traversing the sun is presented, and various hypotheses set forth. It is assumed that this process is responsible for the detection of fewer solar neutrinos than expected, with neutrinos below a minimum energy, E(m), being undetectable. E(m) is found to be about 6 MeV, and the difference of the squares of the respective neutrino masses is calculated to be 6 X 10 to the - 5th sq eV. A restriction on the neutrino mixing angle is assumed such that the change of density near the crossing point is adiabatic. It is predicted that no resonance conversion of neutrinos will occur in the dense core of supernovae, but conversion of electron neutrinos to mu neutrinos will occur as they escape outward through a density region around 100.

Sterile neutrinos in cosmology

NASA Astrophysics Data System (ADS)

Abazajian, Kevork N.

2017-11-01

Sterile neutrinos are natural extensions to the standard model of particle physics in neutrino mass generation mechanisms. If they are relatively light, less than approximately 10 keV, they can alter cosmology significantly, from the early Universe to the matter and radiation energy density today. Here, we review the cosmological role such light sterile neutrinos can play from the early Universe, including production of keV-scale sterile neutrinos as dark matter candidates, and dynamics of light eV-scale sterile neutrinos during the weakly-coupled active neutrino era. We review proposed signatures of light sterile neutrinos in cosmic microwave background and large scale structure data. We also discuss keV-scale sterile neutrino dark matter decay signatures in X-ray observations, including recent candidate ∼3.5 keV X-ray line detections consistent with the decay of a ∼7 keV sterile neutrino dark matter particle.

Generic Friedberg-Lee symmetry of Dirac neutrinos

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luo Shu; Xing Zhizhong; Li Xin

2008-12-01

We write out the generic Dirac neutrino mass operator which possesses the Friedberg-Lee symmetry and find that its corresponding neutrino mass matrix is asymmetric. Following a simple way to break the Friedberg-Lee symmetry, we calculate the neutrino mass eigenvalues and show that the resultant neutrino mixing pattern is nearly tri-bimaximal. Imposing the Hermitian condition on the neutrino mass matrix, we also show that the simplified ansatz is consistent with current experimental data and favors the normal neutrino mass hierarchy.

Blocking Effects of Human Tau on Squid Giant Synapse Transmission and Its Prevention by T-817 MA

PubMed Central

Moreno, Herman; Choi, Soonwook; Yu, Eunah; Brusco, Janaina; Avila, Jesus; Moreira, Jorge E.; Sugimori, Mutsuyuki; Llinás, Rodolfo R.

2011-01-01

Filamentous tau inclusions are hallmarks of Alzheimer's disease and related neurodegenerative tauopathies, but the molecular mechanisms involved in tau-mediated changes in neuronal function and their possible effects on synaptic transmission are unknown. We have evaluated the effects of human tau protein injected directly into the presynaptic terminal axon of the squid giant synapse, which affords functional, structural, and biochemical analysis of its action on the synaptic release process. Indeed, we have found that at physiological concentration recombinant human tau (h-tau42) becomes phosphorylated, produces a rapid synaptic transmission block, and induces the formation of clusters of aggregated synaptic vesicles in the vicinity of the active zone. Presynaptic voltage clamp recordings demonstrate that h-tau42 does not modify the presynaptic calcium current amplitude or kinetics. Analysis of synaptic noise at the post-synaptic axon following presynaptic h-tau42 microinjection revealed an initial phase of increase spontaneous transmitter release followed by a marked reduction in noise. Finally, systemic administration of T-817MA, a proposed neuro-protective agent, rescued tau-induced synaptic abnormalities. Our results show novel mechanisms of h-tau42 mediated synaptic transmission failure and identify a potential therapeutic agent to treat tau-related neurotoxicity. PMID:21629767

Tau Deficiency Down-Regulated Transcription Factor Orthodenticle Homeobox 2 Expression in the Dopaminergic Neurons in Ventral Tegmental Area and Caused No Obvious Motor Deficits in Mice

PubMed Central

Tang, Xiaolu; Jiao, Luyan; Zheng, Meige; Yan, Yan; Nie, Qi; Wu, Ting; Wan, Xiaomei; Zhang, Guofeng; Li, Yonglin; Wu, Song; Jiang, Bin; Cai, Huaibin; Xu, Pingyi; Duan, Jinhai; Lin, Xian

2018-01-01

Tau protein participates in microtubule stabilization, axonal transport, and protein trafficking. Loss of normal tau function will exert a negative effect. However, current knowledge on the impact of tau deficiency on the motor behavior and related neurobiological changes is controversial. In this study, we examined motor functions and analyzed several proteins implicated in the maintenance of midbrain dopaminergic (DA) neurons (mDANs) function of adult and aged tau+/+, tau+/−, tau−/− mice. We found tau deficiency could not induce significant motor disorders. However, we discovered lower expression levels of transcription factors Orthodenticle homeobox 2 (OTX2) of mDANs in older aged mice. Compared with age-matched tau+/+ mice, there were 54.1% lower (p = 0.0192) OTX2 protein (OTX2-fluorescence intensity) in VTA DA neurons of tau+/−mice and 43.6% lower (p = 0.0249) OTX2 protein in VTA DA neurons of tau−/−mice at 18 months old. Combined with the relevant reports, our results suggested that tau deficiency alone might not be enough to mimic the pathology of Parkinson’s disease. However, OTX2 down-regulation indicates that mDANs of tau-deficient mice will be more sensitive to toxic damage from MPTP. PMID:29337233

Paired Helical Filaments from Alzheimer Disease Brain Induce Intracellular Accumulation of Tau Protein in Aggresomes*

PubMed Central

Santa-Maria, Ismael; Varghese, Merina; Ksiȩżak-Reding, Hanna; Dzhun, Anastasiya; Wang, Jun; Pasinetti, Giulio M.

2012-01-01

Abnormal folding of tau protein leads to the generation of paired helical filaments (PHFs) and neurofibrillary tangles, a key neuropathological feature in Alzheimer disease and tauopathies. A specific anatomical pattern of pathological changes developing in the brain suggests that once tau pathology is initiated it propagates between neighboring neuronal cells, possibly spreading along the axonal network. We studied whether PHFs released from degenerating neurons could be taken up by surrounding cells and promote spreading of tau pathology. Neuronal and non-neuronal cells overexpressing green fluorescent protein-tagged tau (GFP-Tau) were treated with isolated fractions of human Alzheimer disease-derived PHFs for 24 h. We found that cells internalized PHFs through an endocytic mechanism and developed intracellular GFP-Tau aggregates with attributes of aggresomes. This was particularly evident by the perinuclear localization of aggregates and redistribution of the vimentin intermediate filament network and retrograde motor protein dynein. Furthermore, the content of Sarkosyl-insoluble tau, a measure of abnormal tau aggregation, increased 3-fold in PHF-treated cells. An exosome-related mechanism did not appear to be involved in the release of GFP-Tau from untreated cells. The evidence that cells can internalize PHFs, leading to formation of aggresome-like bodies, opens new therapeutic avenues to prevent propagation and spreading of tau pathology. PMID:22496370

Gene knockout of tau expression does not contribute to the pathogenesis of prion disease.

PubMed

Lawson, Victoria A; Klemm, Helen M; Welton, Jeremy M; Masters, Colin L; Crouch, Peter; Cappai, Roberto; Ciccotosto, Giuseppe D

2011-11-01

Prion diseases or transmissible spongiform encephalopathies are a group of fatal and transmissible disorders affecting the central nervous system of humans and animals. The principal agent of prion disease transmission and pathogenesis is proposed to be an abnormal protease-resistant isoform of the normal cellular prion protein. The microtubule-associated protein tau is elevated in patients with Creutzfeldt-Jakob disease. To determine whether tau expression contributes to prion disease pathogenesis, tau knockout and control wild-type mice were infected with the M1000 strain of mouse-adapted human prions. Immunohistochemical analysis for total tau expression in prion-infected wild-type mice indicated tau aggregation in the cytoplasm of a subpopulation of neurons in regions associated with spongiform change. Western immunoblot analysis of brain homogenates revealed a decrease in total tau immunoreactivity and epitope-specific changes in tau phosphorylation. No significant difference in incubation period or other disease features were observed between tau knockout and wild-type mice with clinical prion disease. These results demonstrate that, in this model of prion disease, tau does not contribute to the pathogenesis of prion disease and that changes in the tau protein profile observed in mice with clinical prion disease occurs as a consequence of the prion-induced pathogenesis.

Tau regulates the localization and function of End-binding proteins 1 and 3 in developing neuronal cells.

PubMed

Sayas, Carmen Laura; Tortosa, Elena; Bollati, Flavia; Ramírez-Ríos, Sacnicte; Arnal, Isabelle; Avila, Jesús

2015-06-01

The axonal microtubule-associated protein tau is a well-known regulator of microtubule stability in neurons. However, the putative interplay between tau and End-binding proteins 1 and 3 (EB1/3), the core microtubule plus-end tracking proteins, has not been elucidated yet. Here, we show that a cross-talk between tau and EB1/3 exists in developing neuronal cells. Tau and EBs partially colocalize at extending neurites of N1E-115 neuroblastoma cells and axons of primary hippocampal neurons, as shown by confocal immunofluorescence analyses. Tau down-regulation leads to a reduction of EB1/3 comet length, as observed in shRNA-stably depleted neuroblastoma cells and TAU-/- neurons. EB1/3 localization depends on the expression levels and localization of tau protein. Over-expression of tau at high levels induces EBs relocalization to microtubule bundles at extending neurites of N1E-115 cells. In differentiating primary neurons, tau is required for the proper accumulation of EBs at stretches of microtubule bundles at the medial and distal regions of the axon. Tau interacts with EB proteins, as shown by immunoprecipitation in different non-neuronal and neuronal cells and in whole brain lysates. A tau/EB1 direct interaction was corroborated by in vitro pull-down assays. Fluorescence recovery after photobleaching assays performed in neuroblastoma cells confirmed that tau modulates EB3 cellular mobility. In summary, we provide evidence of a new function of tau as a direct regulator of EB proteins in developing neuronal cells. This cross-talk between a classical microtubule-associated protein and a core microtubule plus-end tracking protein may contribute to the fine-tuned regulation of microtubule dynamics and stability during neuronal differentiation. We describe here a novel function for tau as a direct regulator of End binding (EB) proteins in differentiating neuronal cells. EB1/3 cellular mobility and localization in extending neurites and axons is modulated by tau levels and localization. We provide new evidence of the interplay between classical microtubule-associated proteins (MAPs) and "core" microtubule plus-end tracking proteins (+TIPs) during neuronal development. © 2015 International Society for Neurochemistry.

Vectored Intracerebral Immunization with the Anti-Tau Monoclonal Antibody PHF1 Markedly Reduces Tau Pathology in Mutant Tau Transgenic Mice.

PubMed

Liu, Wencheng; Zhao, Lingzhi; Blackman, Brittany; Parmar, Mayur; Wong, Man Ying; Woo, Thomas; Yu, Fangmin; Chiuchiolo, Maria J; Sondhi, Dolan; Kaminsky, Stephen M; Crystal, Ronald G; Paul, Steven M

2016-12-07

Passive immunization with anti-tau monoclonal antibodies has been shown by several laboratories to reduce age-dependent tau pathology and neurodegeneration in mutant tau transgenic mice. These studies have used repeated high weekly doses of various tau antibodies administered systemically for several months and have reported reduced tau pathology of ∼40-50% in various brain regions. Here we show that direct intrahippocampal administration of the adeno-associated virus (AAV)-vectored anti-phospho-tau antibody PHF1 to P301S tau transgenic mice results in high and durable antibody expression, primarily in neurons. Hippocampal antibody levels achieved after AAV delivery were ∼50-fold more than those reported following repeated systemic administration. In contrast to systemic passive immunization, we observed markedly reduced (≥80-90%) hippocampal insoluble pathological tau species and neurofibrillary tangles following a single dose of AAV-vectored PHF1 compared with mice treated with an AAV-IgG control vector. Moreover, the hippocampal atrophy observed in untreated P301S mice was fully rescued by treatment with the AAV-vectored PHF1 antibody. Vectored passive immunotherapy with an anti-tau monoclonal antibody may represent a viable therapeutic strategy for treating or preventing such tauopathies as frontotemporal dementia, progressive supranuclear palsy, or Alzheimer's disease. We have used an adeno-associated viral (AAV) vector to deliver the genes encoding an anti-phospho-tau monoclonal antibody, PHF1, directly to the brain of mice that develop neurodegeneration due to a tau mutation that causes frontotemporal dementia (FTD). When administered systemically, PHF1 has been shown to modestly reduce tau pathology and neurodegeneration. Since such antibodies do not readily cross the blood-brain barrier, we used an AAV vector to deliver antibody directly to the hippocampus and observed much higher antibody levels and a much greater reduction in tau pathology. Using AAV vectors to deliver antibodies like PHF1 directly to brain may constitute a novel approach to treating various neurodegenerative disorders, such as FTD and Alzheimer's disease. Copyright © 2016 the authors 0270-6474/16/3612425-11$15.00/0.

Neutrino flavor evolution in neutron star mergers

NASA Astrophysics Data System (ADS)

Tian, James Y.; Patwardhan, Amol V.; Fuller, George M.

2017-08-01

We examine the flavor evolution of neutrinos emitted from the disklike remnant (hereafter called "neutrino disk") of a binary neutron star (BNS) merger. We specifically follow the neutrinos emitted from the center of the disk, along the polar axis perpendicular to the equatorial plane. We carried out two-flavor simulations using a variety of different possible initial neutrino luminosities and energy spectra and, for comparison, three-flavor simulations in specific cases. In all simulations, the normal neutrino mass hierarchy was used. The flavor evolution was found to be highly dependent on the initial neutrino luminosities and energy spectra; in particular, we found two broad classes of results depending on the sign of the initial net electron neutrino lepton number (i.e., the number of neutrinos minus the number of antineutrinos). In the antineutrino-dominated case, we found that the matter-neutrino resonance effect dominates, consistent with previous results, whereas in the neutrino-dominated case, a bipolar spectral swap develops. The neutrino-dominated conditions required for this latter result have been realized, e.g., in a BNS merger simulation that employs the "DD2" equation of state for neutron star matter [Phys. Rev. D 93, 044019 (2016), 10.1103/PhysRevD.93.044019]. For this case, in addition to the swap at low energies, a collective Mikheyev-Smirnov-Wolfenstein mechanism generates a high-energy electron neutrino tail. The enhanced population of high-energy electron neutrinos in this scenario could have implications for the prospects of r -process nucleosynthesis in the material ejected outside the plane of the neutrino disk.

Probing secret interactions of eV-scale sterile neutrinos with the diffuse supernova neutrino background

NASA Astrophysics Data System (ADS)

Jeong, Yu Seon; Palomares-Ruiz, Sergio; Hall Reno, Mary; Sarcevic, Ina

2018-06-01

Sterile neutrinos with mass in the eV-scale and large mixings of order θ0simeq 0.1 could explain some anomalies found in short-baseline neutrino oscillation data. Here, we revisit a neutrino portal scenario in which eV-scale sterile neutrinos have self-interactions via a new gauge vector boson phi. Their production in the early Universe via mixing with active neutrinos can be suppressed by the induced effective potential in the sterile sector. We study how different cosmological observations can constrain this model, in terms of the mass of the new gauge boson, Mphi, and its coupling to sterile neutrinos, gs. Then, we explore how to probe part of the allowed parameter space of this particular model with future observations of the diffuse supernova neutrino background by the Hyper-Kamiokande and DUNE detectors. For Mphi ~ 5‑10 keV and gs ~ 10‑4‑10‑2, as allowed by cosmological constraints, we find that interactions of diffuse supernova neutrinos with relic sterile neutrinos on their way to the Earth would result in significant dips in the neutrino spectrum which would produce unique features in the event spectra observed in these detectors.

Neutrino Oscillations: Eighty Years in Review

NASA Astrophysics Data System (ADS)

Bowers, Rebecca Lyn

In order to discuss neutrino oscillations, it is necessary to have knowledge of the developments in the field spanning the last eighty years. The existence of the neutrino was posited by Wolfgang Pauli in 1930 to account for the mass defect in beta decay, and to this day physicists are still endeavoring to answer fundamental questions about this enigmatic particle. The scope of this thesis includes a historical background of neutrino physics and a discussion of neutrinos and the Standard Model; subsequent to this is a discussion of the Solar Neutrino Problem, which provided the impetus for the proposal of neutrino oscillations. Bolstering the theory of neutrino oscillations (which is developed in the body of this thesis) are neutrino detector experiments and their results; these include the Homestake experiment, SNO, Kamiokande and Super-Kamiokande, MINOS, and Double-Chooz. We also include relevant derivations, most particularly of the quantum mechanics of neutrino oscillations as treated in the wave packet formalism. We have amassed here the principle theories and experimental results -- a mere tip of the iceberg -- that have brought us to our current understanding of neutrino oscillations. We have also studied the quantum mechanics of neutrino oscillations and developed for ourselves the wave packet formalism describing the phenomenon.

Measurement of the Charged-Current Quasi-Elastic Cross-Section for Electron Neutrinos on a Hydrocarbon Target

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wolcott, Jeremy

2016-01-01

Appearance-type neutrino oscillation experiments, which observe the transition from muon neutrinos to electron neutrinos, promise to help answer some of the fundamental questions surrounding physics in the post-Standard-Model era. Because they wish to observe the interactions of electron neutrinos in their detectors, and because the power of current results is typically limited by their systematic uncertainties, these experiments require precise estimates of the cross-section for electron neutrino interactions. Of particular interest is the charged-current quasi-elastic (CCQE) process, which gures signi cantly in the composition of the reactions observed at the far detector. However, no experimental measurements of this crosssection currentlymore » exist for electron neutrinos; instead, current experiments typically work from the abundance of muon neutrino CCQE cross-section data and apply corrections from theoretical arguments to obtain a prediction for electron neutrinos. Veri cation of these predictions is challenging due to the di culty of constructing an electron neutrino beam, but the advent of modern high-intensity muon neutrino beams|together with the percent-level electron neutrino impurity inherent in these beams| nally presents the opportunity to make such a measurement. We report herein the rst-ever measurement of a cross-section for an exclusive state in electron neutrino scattering, which was made using the MINER A detector in the NuMI neutrino beam at Fermilab. We present the electron neutrino CCQE di erential cross-sections, which are averaged over neutrinos of energies 1-10 GeV (with mean energy of about 3 GeV), in terms of various kinematic variables: nal-state electron angle, nal-state electron energy, and the square of the fourmomentum transferred to the nucleus by the neutrino , Q 2. We also provide a total cross-section vs. neutrino energy. While our measurement of this process is found to be in agreement with the predictions of the GENIE event generator, we also report on an unpredicted photon-like process we observe in a similar kinematic regime. The absence of this process from models for neutrino interactions is a potential stumbling block for future on-axis neutrino oscillation experiments. We include kinematic and particle species identi cation characterizations which can be used in building models to help address this shortcoming.« less

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. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

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

Caspase-2 cleavage of tau reversibly impairs memory.

PubMed

Zhao, Xiaohui; Kotilinek, Linda A; Smith, Benjamin; Hlynialuk, Chris; Zahs, Kathleen; Ramsden, Martin; Cleary, James; Ashe, Karen H

2016-11-01

In Alzheimer's disease (AD) and other tauopathies, the tau protein forms fibrils, which are believed to be neurotoxic. However, fibrillar tau has been dissociated from neuron death and network dysfunction, suggesting the involvement of nonfibrillar species. Here we describe a novel pathological process in which caspase-2 cleavage of tau at Asp314 impairs cognitive and synaptic function in animal and cellular models of tauopathies by promoting the missorting of tau to dendritic spines. The truncation product, Δtau314, resists fibrillation and is present at higher levels in brains from cognitively impaired mice and humans with AD. The expression of tau mutants that resisted caspase-2 cleavage prevented tau from infiltrating spines, dislocating glutamate receptors and impairing synaptic function in cultured neurons, and it prevented memory deficits and neurodegeneration in mice. Decreasing the levels of caspase-2 restored long-term memory in mice that had existing deficits. Our results suggest an overall treatment strategy for re-establishing synaptic function and restoring memory in patients with AD by preventing tau from accumulating in dendritic spines.

Some Unsettled Questions in the Problem of Neutrino Oscillations. Experiments

NASA Astrophysics Data System (ADS)

Muchamedovich Beshtoev, Khamidbi

2003-07-01

It is shown that in order to register neutrino oscillations, it is necessary to see second or higher neutrino oscillation modes on experiments. For this purpose we can use the elliptic character of 1the Earth orbit. A special importance for study of the Earth neutrino sources, using big neutrino detectors, is stressed here. The analysis is showing that the SNO experimental results do not confirm the smallest of νe → ντ transition angle mixings, which was obtained from analysis of the CHOOZ experimental data. It is also noted that there is contradiction between SNO, super-Kamiokande, Homestake and the SAGE and GNO (GALLEX) data. 1. Introduction In this article we will consider some unsettled questions in experiments on the problem of neutrino oscillations. 2. experimental Observation of the Neutrino Oscillations At present it supposed that the neutrino oscillations have been observed [1-3], In reality in these experiments there were observed only transitions between (the Sun or atmospheric) neutrinos. Since we presume that the neutrino oscillations do take place; therefore we must observe (Sun) neutrino oscillations in reality. Since the length of neutrino oscillations is great sufficiently, we cannot observe the higher modes in terrestrial experiment. But we have another possibility to observe the Sun neutrino oscillation using the fact that the Earth orbit is the elliptic one with: Earth's perihelion RP = 147.117 ·106k m , Earth's aphelion RA = 152.083 ·106k m, and their difference R is R = 4.866 · 106 k m. Since the Sun neutrinos conclude all energies up to 15M eV , we must divide this energy spectrum into energy regions and observe these neutrino fluxes as a function of energy and the Ears's distances from the Sun. At these conditions we must observe the neutrino oscillations, in order to determine if the length of neutrino oscillation Rosc is bigger than the region where these (high energy)

Rapid Neurofibrillary Tangle Formation after Localized Gene Transfer of Mutated Tau

PubMed Central

Klein, Ronald L.; Lin, Wen-Lang; Dickson, Dennis W.; Lewis, Jada; Hutton, Michael; Duff, Karen; Meyer, Edwin M.; King, Michael A.

2004-01-01

Neurofibrillary pathology was produced in the brains of adult rats after localized gene transfer of human tau carrying the P301L mutation, which is associated with frontotemporal dementia with parkinsonism. Within 1 month of in situ transfection of the basal forebrain region of normal rats, tau-immunoreactive and argyrophilic neuronal lesions formed. The fibrillar lesions had features of neurofibrillary tangles and tau immunoreactivity at light and electron microscopic levels. In addition to neurofibrillary tangles, other tau pathology, including pretangles and neuropil threads, was abundant and widespread. Tau gene transfer to the hippocampal region of amyloid-depositing transgenic mice produced pretangles and threads, as well as intensely tau-immunoreactive neurites in amyloid plaques. The ability to produce neurofibrillary pathology in adult rodents makes this a useful method to study tau-related neurodegeneration. PMID:14695347

Tau hyperphosphorylation in the brain of ob/ob mice is due to hypothermia: Importance of thermoregulation in linking diabetes and Alzheimer's disease.

PubMed

Gratuze, Maud; El Khoury, Noura B; Turgeon, Andréanne; Julien, Carl; Marcouiller, François; Morin, Françoise; Whittington, Robert A; Marette, André; Calon, Frédéric; Planel, Emmanuel

2017-02-01

Over the last few decades, there has been a significant increase in epidemiological studies suggesting that type 2 diabetes (T2DM) is linked to a higher risk of Alzheimer's disease (AD). However, how T2DM affects AD pathology, such as tau hyperphosphorylation, is not well understood. In this study, we investigated the impact of T2DM on tau phosphorylation in ob/ob mice, a spontaneous genetic model of T2DM. Tau phosphorylation at the AT8 epitope was slightly elevated in 4-week-old ob/ob mice while 26-week-old ob/ob mice exhibited tau hyperphosphorylation at multiple tau phospho-epitopes (Tau1, CP13, AT8, AT180, PHF1). We then examined the mechanism of tau hyperphosphorylation and demonstrated that it is mostly due to hypothermia, as ob/ob mice were hypothermic and normothermia restored tau phosphorylation to control levels. As caffeine has been shown to be beneficial for diabetes, obesity and tau phosphorylation, we, therefore, used it as therapeutic treatment. Unexpectedly, chronic caffeine intake exacerbated tau hyperphosphorylation by promoting deeper hypothermia. Our data indicate that tau hyperphosphorylation is predominately due to hypothermia consequent to impaired thermoregulation in ob/ob mice. This study establishes a novel link between diabetes and AD, and reinforces the importance of recording body temperature to better assess the relationship between diabetes and AD. Copyright © 2016 Elsevier Inc. All rights reserved.

Passive Immunization with Anti-Tau Antibodies in Two Transgenic Models

PubMed Central

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

2011-01-01

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. PMID:21841002

Beneficial effects of exercise in a transgenic mouse model of Alzheimer's disease-like Tau pathology.

PubMed

Belarbi, Karim; Burnouf, Sylvie; Fernandez-Gomez, Francisco-Jose; Laurent, Cyril; Lestavel, Sophie; Figeac, Martin; Sultan, Audrey; Troquier, Laetitia; Leboucher, Antoine; Caillierez, Raphaëlle; Grosjean, Marie-Eve; Demeyer, Dominique; Obriot, Hélène; Brion, Ingrid; Barbot, Bérangère; Galas, Marie-Christine; Staels, Bart; Humez, Sandrine; Sergeant, Nicolas; Schraen-Maschke, Susanna; Muhr-Tailleux, Anne; Hamdane, Malika; Buée, Luc; Blum, David

2011-08-01

Tau pathology is encountered in many neurodegenerative disorders known as tauopathies, including Alzheimer's disease. Physical activity is a lifestyle factor affecting processes crucial for memory and synaptic plasticity. Whether long-term voluntary exercise has an impact on Tau pathology and its pathophysiological consequences is currently unknown. To address this question, we investigated the effects of long-term voluntary exercise in the THY-Tau22 transgenic model of Alzheimer's disease-like Tau pathology, characterized by the progressive development of Tau pathology, cholinergic alterations and subsequent memory impairments. Three-month-old THY-Tau22 mice and wild-type littermates were assigned to standard housing or housing supplemented with a running wheel. After 9 months of exercise, mice were evaluated for memory performance and examined for hippocampal Tau pathology, cholinergic defects, inflammation and genes related to cholesterol metabolism. Exercise prevented memory alterations in THY-Tau22 mice. This was accompanied by a decrease in hippocampal Tau pathology and a prevention of the loss of expression of choline acetyltransferase within the medial septum. Whereas the expression of most cholesterol-related genes remained unchanged in the hippocampus of running THY-Tau22 mice, we observed a significant upregulation in mRNA levels of NPC1 and NPC2, genes involved in cholesterol trafficking from the lysosomes. Our data support the view that long-term voluntary physical exercise is an effective strategy capable of mitigating Tau pathology and its pathophysiological consequences. Copyright © 2011 Elsevier Inc. All rights reserved.

Hardron production and neutrino beams

NASA Astrophysics Data System (ADS)

Guglielmi, A.

2006-11-01

The precise measurements of the neutrino mixing parameters in the oscillation experiments at accelerators require new high-intensity and high-purity neutrino beams. Ancillary hadron-production measurements are then needed as inputs to precise calculation of neutrino beams and of atmospheric neutrino fluxes.

Solar atmospheric neutrinos: A new neutrino floor for dark matter searches

NASA Astrophysics Data System (ADS)

Ng, Kenny C. Y.; Beacom, John F.; Peter, Annika H. G.; Rott, Carsten

2017-11-01

As is well known, dark matter direct detection experiments will ultimately be limited by a "neutrino floor," due to the scattering of nuclei by MeV neutrinos from, e.g., nuclear fusion in the Sun. Here we point out the existence of a new neutrino floor that will similarly limit indirect detection with the Sun, due to high-energy neutrinos from cosmic-ray interactions with the solar atmosphere. We have two key findings. First, solar atmospheric neutrinos ≲1 TeV cause a sensitivity floor for standard weakly interacting massive particles (WIMP) scenarios, for which higher-energy neutrinos are absorbed in the Sun. This floor will be reached once the present sensitivity is improved by just 1 order of magnitude. Second, for neutrinos ≳1 TeV , which can be isolated by muon energy loss rate, solar atmospheric neutrinos should soon be detectable in IceCube. Discovery will help probe the complicated effects of solar magnetic fields on cosmic rays. These events will be backgrounds to WIMP scenarios with long-lived mediators, for which higher-energy neutrinos can escape from the Sun.

Demystifying the PeV cascades in IceCube: Less (energy) is more (events)

NASA Astrophysics Data System (ADS)

Laha, Ranjan; Beacom, John F.; Dasgupta, Basudeb; Horiuchi, Shunsaku; Murase, Kohta

2013-08-01

The IceCube neutrino observatory has detected two cascade events with energies near 1 PeV [A. Ishihara Proceedings of Neutrino 2012 Conference, http://neu2012.kek.jp/index.html; M. Aartsen et al. (IceCube Collaboration) Phys. Rev. Lett. 111, 021103 (2013)]. Without invoking new physics, we analyze the source of these neutrinos. We show that atmospheric conventional neutrinos and cosmogenic neutrinos (those produced in the propagation of ultra-high-energy cosmic rays) are strongly disfavored. For atmospheric prompt neutrinos or a diffuse background of neutrinos produced in astrophysical objects, the situation is less clear. We show that there is tension with observed data, but that the details depend on the least-known aspects of the IceCube analysis. Very likely, prompt neutrinos are disfavored and astrophysical neutrinos are plausible. We demonstrate that the fastest way to reveal the origin of the observed PeV neutrinos is to search for neutrino cascades in the range below 1 PeV, for which dedicated analyses with high sensitivity have yet to appear, and where many more events could be found.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Coloma, Pilar; Peres, Orlando G.

If the heaviest neutrino mass eigenstate is unstable, its decay modes could include lighter neutrino eigenstates. In this case part of the decay products could be visible, as they would interact at neutrino detectors via mixing. At neutrino oscillation experiments, a characteristic signature of such \\emph{visible neutrino decay} would be an apparent excess of events at low energies. We focus on a simple phenomenological model in which the heaviest neutrino decays asmore » $$\

Influence of flavor oscillations on neutrino beam instabilities

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mendonça, J. T., E-mail: titomend@ist.utl.pt; Haas, F.; Bret, A.

2014-09-15

We consider the collective neutrino plasma interactions and study the electron plasma instabilities produced by a nearly mono-energetic neutrino beam in a plasma. We describe the mutual interaction between neutrino flavor oscillations and electron plasma waves. We show that the neutrino flavor oscillations are not only perturbed by electron plasmas waves but also contribute to the dispersion relation and the growth rates of neutrino beam instabilities.

Abnormally phosphorylated tau protein in senile dementia of Lewy body type and Alzheimer disease: evidence that the disorders are distinct.

PubMed

Strong, C; Anderton, B H; Perry, R H; Perry, E K; Ince, P G; Lovestone, S

1995-01-01

The relationship between Alzheimer disease (AD) and dementia with Lewy bodies (senile dementia Lewy body type, or SDLT) and dementia in Parkinson's disease is unclear. AD pathology is characterised by both amyloid deposition and abnormal phosphorylation of tau in paired helical filaments (PHF-tau). In AD, abnormally phosphorylated PHF-tau is present in neurofibrillary tangles, in neuritic processes of senile plaques, and also in neuropil threads dispersed throughout the cerebral cortex. Cortical homogenates from 12 cases each of AD and SDLT, 13 cases of Parkinson's disease, and 11 normal controls were examined by Western blot analysis with antibodies that detect PHF-tau. No PHF-tau was found in Parkinson's disease or control cortex. No PHF-tau was found in SDLT cases without histological evidence of tangles. PHF-tau was detectable in SDLT cases with a low density of tangles, and large amounts of PHF-tau were present in AD cases. This study demonstrates that abnormally phosphorylated PHF-tau is only present where tangles are found and not in SDLT cases without tangles or with only occasional tangles. It is concluded that Lewy body dementias are distinct at a molecular level from AD.

The novel Tau mutation G335S: clinical, neuropathological and molecular characterization.

PubMed

Spina, Salvatore; Murrell, Jill R; Yoshida, Hirotaka; Ghetti, Bernardino; Bermingham, Niamh; Sweeney, Brian; Dlouhy, Stephen R; Crowther, R Anthony; Goedert, Michel; Keohane, Catherine

2007-04-01

Mutations in Tau cause the inherited neurodegenerative disease, frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17). Known coding region mutations cluster in the microtubule-binding region, where they alter the ability of tau to promote microtubule assembly. Depending on the tau isoforms, this region consists of three or four imperfect repeats of 31 or 32 amino acids, each of which contains a characteristic and invariant PGGG motif. Here, we report the novel G335S mutation, which changes the PGGG motif of the third tau repeat to PGGS, in an individual who developed social withdrawal, emotional bluntness and stereotypic behavior at age 22, followed by disinhibition, hyperorality and ideomotor apraxia. Abundant tau-positive inclusions were present in neurons and glia in the frontotemporal cortex, hippocampus and brainstem. Sarkosyl-insoluble tau showed paired helical and straight filaments, as well as more irregular rope-like filaments. The pattern of pathological tau bands was like that of Alzheimer disease. Experimentally, the G335S mutation resulted in a greatly reduced ability of tau to promote microtubule assembly, while having no significant effect on heparin-induced assembly of recombinant tau into filaments.

Dexmedetomidine increases tau phosphorylation under normothermic conditions in vivo and in vitro.

PubMed

Whittington, Robert A; Virág, László; Gratuze, Maud; Petry, Franck R; Noël, Anastasia; Poitras, Isabelle; Truchetti, Geoffrey; Marcouiller, François; Papon, Marie-Amélie; El Khoury, Noura; Wong, Kevin; Bretteville, Alexis; Morin, Françoise; Planel, Emmanuel

2015-08-01

There is developing interest in the potential association between anesthesia and the onset and progression of Alzheimer's disease. Several anesthetics have, thus, been demonstrated to induce tau hyperphosphorylation, an effect mostly mediated by anesthesia-induced hypothermia. Here, we tested the hypothesis that acute normothermic administration of dexmedetomidine (Dex), an intravenous sedative used in intensive care units, would result in tau hyperphosphorylation in vivo and in vitro. When administered to nontransgenic mice, Dex-induced tau hyperphosphorylation persisting up to 6 hours in the hippocampus for the AT8 epitope. Pretreatment with atipamezole, a highly specific α2-adrenergic receptor antagonist, blocked Dex-induced tau hyperphosphorylation. Furthermore, Dex dose-dependently increased tau phosphorylation at AT8 in SH-SY5Y cells, impaired mice spatial memory in the Barnes maze and promoted tau hyperphosphorylation and aggregation in transgenic hTau mice. These findings suggest that Dex: (1) increases tau phosphorylation, in vivo and in vitro, in the absence of anesthetic-induced hypothermia and through α2-adrenergic receptor activation, (2) promotes tau aggregation in a mouse model of tauopathy, and (3) impacts spatial reference memory. Copyright © 2015 Elsevier Inc. All rights reserved.

Tau regulates the subcellular localization of calmodulin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barreda, Elena Gomez de; Avila, Jesus, E-mail: javila@cbm.uam.es; CIBER de Enfermedades Neurodegenerativas, 28031 Madrid

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 amore » 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.« less

Progressive Motor Deficit is Mediated by the Denervation of Neuromuscular Junctions and Axonal Degeneration in Transgenic Mice Expressing Mutant (P301S) Tau Protein.

PubMed

Yin, Zhuoran; Valkenburg, Femke; Hornix, Betty E; Mantingh-Otter, Ietje; Zhou, Xingdong; Mari, Muriel; Reggiori, Fulvio; Van Dam, Debby; Eggen, Bart J L; De Deyn, Peter P; Boddeke, Erik

2017-01-01

Tauopathies include a variety of neurodegenerative diseases associated with the pathological aggregation of hyperphosphorylated tau, resulting in progressive cognitive decline and motor impairment. The underlying mechanism for motor deficits related to tauopathy is not yet fully understood. Here, we use a novel transgenic tau mouse line, Tau 58/4, with enhanced neuron-specific expression of P301S mutant tau to investigate the motor abnormalities in association with the peripheral nervous system. Using stationary beam, gait, and rotarod tests, motor deficits were found in Tau 58/4 mice already 3 months after birth, which deteriorated during aging. Hyperphosphorylated tau was detected in the cell bodies and axons of motor neurons. At the age of 9 and 12 months, significant denervation of the neuromuscular junction in the extensor digitorum longus muscle was observed in Tau 58/4 mice, compared to wild-type mice. Muscle hypotrophy was observed in Tau 58/4 mice at 9 and 12 months. Using electron microscopy, we observed ultrastructural changes in the sciatic nerve of 12-month-old Tau 58/4 mice indicative of the loss of large axonal fibers and hypomyelination (assessed by g-ratio). We conclude that the accumulated hyperphosphorylated tau in the axon terminals may induce dying-back axonal degeneration, myelin abnormalities, neuromuscular junction denervation, and muscular atrophy, which may be the mechanisms responsible for the deterioration of the motor function in Tau 58/4 mice. Tau 58/4 mice represent an interesting neuromuscular degeneration model, and the pathological mechanisms might be responsible for motor signs observed in some human tauopathies.

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

Tau hyperphosphorylation and deregulation of calcineurin in mouse models of Huntington's disease.

PubMed

Gratuze, Maud; Noël, Anastasia; Julien, Carl; Cisbani, Giulia; Milot-Rousseau, Philippe; Morin, Françoise; Dickler, Maya; Goupil, Claudia; Bezeau, François; Poitras, Isabelle; Bissonnette, Stéphanie; Whittington, Robert A; Hébert, Sébastien S; Cicchetti, Francesca; Parker, J Alex; Samadi, Pershia; Planel, Emmanuel

2015-01-01

Huntington's disease (HD) is an autosomal-dominant neurodegenerative disorder caused by polyglutamine expansions in the amino-terminal region of the huntingtin (Htt) protein. At the cellular level, neuronal death is accompanied by the proteolytic cleavage, misfolding and aggregation of huntingtin. Abnormal hyperphosphorylation of tau protein is a characteristic feature of a class of neurodegenerative diseases called tauopathies. As a number of studies have reported tau pathology in HD patients, we investigated whether HD pathology may promote tau hyperphosphorylation and if so tackle some of its underlying mechanisms. For that purpose, we used the R6/2 mouse, a well-characterized model of HD, and analyzed tau phosphorylation before and after the onset of HD-like symptoms. We found a significant increase in tau hyperphosphorylation at the PHF-1 epitope in pre-symptomatic R6/2 mice, whereas symptomatic mice displayed tau hyperphosphorylation at multiple tau phosphoepitopes (AT8, CP13, PT205 and PHF-1). There was no activation of major tau kinases that could explain this observation. However, when we examined tau phosphatases, we found that calcineurin/PP2B was downregulated by 30% in pre-symptomatic and 50% in symptomatic R6/2 mice, respectively. We observed similar changes in tau phosphorylation and calcineurin expression in Q175 mice, another HD model. Calcineurin was also reduced in Q111 compared with Q7 cells. Finally, pharmacological or genetic inhibition of endogenous calcineurin was sufficient to promote tau hyperphosphorylation in neuronal cells. Taken together, our data suggest that mutant huntingtin can induce abnormal tau hyperphosphorylation in vivo, via the deregulation of calcineurin. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Pretangles and neurofibrillary changes: similarities and differences between AD and CBD based on molecular and morphological evolution.

PubMed

Uchihara, Toshiki

2014-12-01

Pretangles are cytoplasmic tau immunoreactivity in neurons without apparent formation of fibrillary structures. In Alzheimer disease, such tau deposition is considered to represent a premature state prior to fibril formation (AD-pretangles), later to form neurofibrillary tangles and finally ghost tangles. This morphological evolution from pretangles to ghost tangles is in parallel with their profile shift from four repeat (4R) tau-positive pretangles to three repeat (3R) tau-positive ghost tangles with both positive neurofibrillary tangles in between. This complementary shift of tau profile from 4R to 3R suggests that these tau epitopes are represented interchangeably along tangle evolution. Similar tau immunoreactivity without fibril formation is also observed in corticobasal degeneration (CBD-pretangles). CBD-pretangles and AD-pretangles share: (i) selective 4R tau immunoreactivity without involvement of 3R tau; and (ii) argyrophilia with Gallyas silver impregnation. However, CBD-pretangles neither evolve into ghost tangles nor exhibit 3R tau immunoreactivity even at the advanced stage. Because electron microscopic studies on these pretangles are quite limited, it remains to be clarified whether such differences in later evolution are related to their primary ultrastructures, potentially distinct between AD and CBD. As double staining for 3R and 4R tau clarified complementary shift from 4R to 3R tau along evolution from pretangles to ghost tangles, double immunoelectron microscopy, if possible, may clarify similar profile shifts in relation to each tau fibril at the ultrastructural dimension. This will provide a unique viewpoint on how molecular (epitope) representations are related to pathogenesis of fibrillary components. © 2014 Japanese Society of Neuropathology.

Developmental exposure to lead (Pb) alters the expression of the human tau gene and its products in a transgenic animal model

PubMed Central

Dash, M.; Eid, A.; Subaiea, G.; Chang, J.; Deeb, R.; Masoud, A.; Renehan, W.E.; Adem, A.; Zawia, N.H.

2016-01-01

Tauopathies are a class of neurodegenerative diseases associated with the pathological aggregationof the tau protein in the human brain. The best known of these illnesses is Alzheimer's disease (AD); a disease where the microtubule associated protein tau (MAPT) becomes hyperphosphorylated (lowering its binding affinity to microtubules) and aggregates within neurons in the form of neurofibrillary tangles (NFTs). In this paper we examine whether environmental factors play a significant role in tau pathogenesis. Our studies were conducted in a double mutant mouse model that expressed the human tau gene and lacked the gene for murine tau. The human tau mouse model was tested for the transgene's ability to respond to an environmental toxicant. Pups were developmentally exposed to lead (Pb) from postnatal day (PND) 1-20 with 0.2% Pb acetate. Mice were then sacrificed at PND 20, 30, 40 and 60. Protein and mRNA levels for tau and CDK5 as well as tau phosphorylation at Ser396 were determined. In addition, the potential role of miRNA in tau expression was investigated by measuring levels of miR-34c, a miRNA that targets the mRNA for human tau, at PND20 and 50. The expression of the human tau transgene was altered by developmental exposure to Pb. This exposure also altered the expression of miR-34c. Our findings are the first of their kind to test the responsiveness of the human tau gene to an environmental toxicant and to examine an epigenetic mechanism that may be involved in the regulation of this gene's expression. PMID:27293183

Hippocampal tau pathology is related to neuroanatomical connections: an ageing population-based study.

PubMed

Lace, G; Savva, G M; Forster, G; de Silva, R; Brayne, C; Matthews, F E; Barclay, J J; Dakin, L; Ince, P G; Wharton, S B

2009-05-01

Deposits of abnormally phosphorylated tau protein are found in numerous neurodegenerative disorders; the 'tauopathies', which include Alzheimer's and Pick's diseases, but tau pathology is also found in the ageing brain. Variation in tau pathology in brain ageing and its relationship to development of tauopathies and cognitive impairment remains unclear. We aimed to determine the extent and pattern of spread of tau pathology in the hippocampus, a susceptible region important in dementia and milder states of memory impairment, using hippocampal samples from the elderly population-based Medical Research Council Cognitive Function and Ageing Study neuropathology cohort. Tau deposition was assessed in hippocampal anatomical sub-regions using the AT8 antibody to phosphorylated tau and isoform-specific antibodies to 3 and 4-repeat tau (RD3 and RD4). Abeta pathology was also assessed. In this population sample, which includes the full ageing spectrum from individuals with no cognitive impairment to those with dementia satisfying clinico-pathology criteria for Alzheimer's disease, we have demonstrated a high prevalence at death of tau pathology. AT8, Abeta, RD3 and RD4 showed similar regional distribution and increased RD3 was noted in late-stage ghost tangles. Abeta was shown to be a poor explanatory variable for tau pathology. Tau deposition progressed in a hierarchical manner. Hippocampal input regions and projection zones (such as lateral entorhinal cortex, CA1/subiculum border and outer molecular layer of dentate) were initially affected, with anterograde progression though the hippocampal circuitry. Six hippocampal tau anatomical stages were defined, each linking projectionally to their adjacent stages, suggesting spread of tau malfunction through neuroanatomical pathways in hippocampal ageing. These stages were significantly associated with dementia, and may provide a clinically useful tool in the clinico-pathological assessment of dementia and mild cognitive impairment.

Alzheimer's amyloid-β oligomers rescue cellular prion protein induced tau reduction via the Fyn pathway.

PubMed

Chen, Rong-Jie; Chang, Wei-Wei; Lin, Yu-Chun; Cheng, Pei-Lin; Chen, Yun-Ru

2013-09-18

Amyloid-β (Aβ) and tau are the pathogenic hallmarks in Alzheimer's disease (AD). Aβ oligomers are considered the actual toxic entities, and the toxicity relies on the presence of tau. Recently, Aβ oligomers have been shown to specifically interact with cellular prion protein (PrP(C)) where the role of PrP(C) in AD is still not fully understood. To investigate the downstream mechanism of PrP(C) and Aβ oligomer interaction and their possible relationships to tau, we examined tau expression in human neuroblastoma BE(2)-C cells transfected with murine PrP(C) and studied the effect under Aβ oligomer treatment. By Western blotting, we found that PrP(C) overexpression down-regulated tau protein and Aβ oligomer binding alleviated the tau reduction induced by wild type but not M128V PrP(C), the high AD risk polymorphic allele in human prion gene. PrP(C) lacking the Aβ oligomer binding site was incapable of rescuing the level of tau reduction. Quantitative RT-PCR showed the PrP(C) effect was attributed to tau reduction at the transcription level. Treatment with Fyn pathway inhibitors, Fyn kinase inhibitor PP2 and MEK inhibitor U0126, reversed the PrP(C)-induced tau reduction and Aβ oligomer treatment modulated Fyn kinase activity. The results suggested Fyn pathway regulated Aβ-PrP(C)-tau signaling. Overall, our results demonstrated that PrP(C) down-regulated tau via the Fyn pathway and the effect can be regulated by Aβ oligomers. Our study facilitated the understanding of molecular mechanisms among PrP(C), tau, and Aβ oligomers.

New physics with ultra-high-energy neutrinos

DOE PAGES

Marfatia, D.; McKay, D. W.; Weiler, T. J.

2015-07-03

Now that PeV neutrinos have been discovered by IceCube, we optimistically entertain the possibility that neutrinos with energy above 100PeV exist. Here, we evaluate the dependence of event rates of such neutrinos on the neutrino-nucleon cross section at observatories that detect particles, atmospheric fluorescence, or Cherenkov radiation, initiated by neutrino interactions. We consider how (i)a simple scaling of the total standard model neutrino-nucleon cross section, (ii) a new elastic neutral current interaction, and (iii) anew completely inelastic interaction, individually impact event rates.

Distinguishing neutrino mass hierarchies using dark matter annihilation signals at IceCube

DOE Office of Scientific and Technical Information (OSTI.GOV)

Allahverdi, Rouzbeh; Knockel, Bradley; Dutta, Bhaskar

2015-12-01

We explore the possibility of distinguishing neutrino mass hierarchies through the neutrino signal from dark matter annihilation at neutrino telescopes. We consider a simple extension of the standard model where the neutrino masses and mixing angles are obtained via the type-II seesaw mechanism as an explicit example. We show that future extensions of IceCube neutrino telescope may detect the neutrino signal from DM annihilation at the Galactic Center and inside the Sun, and differentiate between the normal and inverted mass hierarchies, in this model.

Late time neutrino masses, the LSND experiment, and the cosmic microwave background.

PubMed

Chacko, Z; Hall, Lawrence J; Oliver, Steven J; Perelstein, Maxim

2005-03-25

Models with low-scale breaking of global symmetries in the neutrino sector provide an alternative to the seesaw mechanism for understanding why neutrinos are light. Such models can easily incorporate light sterile neutrinos required by the Liquid Scintillator Neutrino Detector experiment. Furthermore, the constraints on the sterile neutrino properties from nucleosynthesis and large-scale structure can be removed due to the nonconventional cosmological evolution of neutrino masses and densities. We present explicit, fully realistic supersymmetric models, and discuss the characteristic signatures predicted in the angular distributions of the cosmic microwave background.

Neutrino Physics at Fermilab

ScienceCinema

Saoulidou, Niki

2017-12-09

Neutrino oscillations provide the first evidence for physics beyond the Standard Model. I will briefly overview the neutrino "hi-story", describing key discoveries over the past decades that shaped our understanding of neutrinos and their behavior. Fermilab was, is and hopefully will be at the forefront of the accelerator neutrino experiments.  NuMI, the most powerful accelerator neutrino beam in the world has ushered us into the era of precise measurements. Its further upgrades may give a chance to tackle the remaining mysteries of the neutrino mass hierarchy and possible CP violation.

Active-sterile neutrino conversion: consequences for the r-process and supernova neutrino detection

NASA Astrophysics Data System (ADS)

Fetter, J.; McLaughlin, G. C.; Balantekin, A. B.; Fuller, G. M.

2003-02-01

We examine active-sterile neutrino conversion in the late time post-core-bounce supernova environment. By including the effect of feedback on the Mikheyev-Smirnov-Wolfenstein (MSW) conversion potential, we obtain a large range of neutrino mixing parameters which produce a favorable environment for the r-process. We look at the signature of this effect in the current generation of neutrino detectors now coming on line. We also investigate the impact of the neutrino-neutrino forward-scattering-induced potential on the MSW conversion.

Estudo da Oscilação de Neutrinos Muônicos Usando Dados Atmosféricos e de Acelerador nos Experimentos MINOS e MINOS+

DOE Office of Scientific and Technical Information (OSTI.GOV)

Medeiros, Michelle Mesquita de

The MINOS (Main Injector Neutrino Oscillation Search) and MINOS+ experiments were designed to study neutrino oscillations using a muon neutrino beam which is detected in two different locations, in the Near Detector and in the Far Detector. The distance between the detectors allows the beam neutrinos to oscillate to a different flavor. Therefore, a disappearance of the muon neutrinos from the beam is observed in the Far Detector. The Far Detector has a special apparatus which makes possible the selection of atmospheric neutrinos and antineutrinos. These come from interactions of cosmic rays with the Earth’s atmosphere. Both detectors have amore » magnetic field, allowing the distiction between neutrinos and antineutrinos interactions. This thesis presents the first combined analysis of data from the MINOS and MINOS+ experiments. We have analyzed the combined neutrino energy spectrum from the complete MINOS beam data and the first, more energetic, MINOS+ beam data. The disappearance of the muon neutrinos was observed and the data has shown to be congruent with the oscillation model. Beyond that, we have measured the atmospheric oscillation parameters of the beam and atmospheric neutrinos and antineutrinos from MINOS combined with the atmospheric neutrinos and antineutrinos from MINOS+. Assuming the same oscillation parameters for both neutrinos and antineutrinos, the best fit is obtained for inverted hierarchy and lower octant with Δm 2 32 = 2:37 X 10 -3 eV 2 and sin 2 θ 23 = 0:43, and the limits m 2 32 = [2,29 - 2,49] 10 -3 eV 2 (68%) and sin 2 θ 23 = 0.36 - 0.66 (90%). These results are the most precise measurement of the neutrinos mass splitting using muon neutrino disappearance data only.« less

Impact of Neutrino Flavor Oscillations on the Neutrino-driven Wind Nucleosynthesis of an Electron-capture Supernova

NASA Astrophysics Data System (ADS)

Pllumbi, Else; Tamborra, Irene; Wanajo, Shinya; Janka, Hans-Thomas; Hüdepohl, Lorenz

2015-08-01

Neutrino oscillations, especially to light sterile states, can affect nucleosynthesis yields because of their possible feedback effect on the electron fraction (Ye). For the first time, we perform nucleosynthesis calculations for neutrino-driven wind trajectories from the neutrino-cooling phase of an 8.8 {M}⊙ electron-capture supernova (SN), whose hydrodynamic evolution was computed in spherical symmetry with sophisticated neutrino transport and whose Ye evolution was post-processed by including neutrino oscillations between both active and active-sterile flavors. We also take into account the α-effect as well as weak magnetism and recoil corrections in the neutrino absorption and emission processes. We observe effects on the Ye evolution that depend in a subtle way on the relative radial positions of the sterile Mikheyev-Smirnov-Wolfenstein resonances, on collective flavor transformations, and on the formation of α particles. For the adopted SN progenitor, we find that neutrino oscillations, also to a sterile state with eV mass, do not significantly affect the element formation and in particular cannot make the post-explosion wind outflow neutron-rich enough to activate a strong r-process. Our conclusions become even more robust when, in order to mimic equation-of-state-dependent corrections due to nucleon potential effects in the dense-medium neutrino opacities, six cases with reduced Ye in the wind are considered. In these cases, despite the conversion of active neutrinos to sterile neutrinos, Ye increases or is not significantly lowered compared to the values obtained without oscillations and active flavor transformations. This is a consequence of a complicated interplay between sterile-neutrino production, neutrino-neutrino interactions, and α-effect.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aranda, J. I.; Tututi, E. S.; Ramirez-Zavaleta, F.

The size of the branching ratios for the {tau}{yields}{mu}{gamma} and {tau}{yields}{mu}{gamma}{gamma} decays induced by a lepton flavor violating Higgs interaction H{tau}{mu} is studied in the framework of effective field theories. The best constraint on the H{tau}{mu} vertex, derived from the know measurement on the muon anomalous magnetic moment, is used to impose the upper bounds Br({tau}{yields}{mu}{gamma})<7.5x10{sup -10} and Br({tau}{yields}{mu}{gamma}{gamma})<2.3x10{sup -12}, which are more stringent than current experimental limits on this class of transitions.

A search for sterile neutrinos with IceCube DeepCore

NASA Astrophysics Data System (ADS)

Terliuk, Andrii; IceCube Collaboration

2017-09-01

The DeepCore detector is a densely instrumented part of the IceCube Neutrino Observatory that lowers the neutrino detection threshold down to approximately 10 GeV resulting in the ability to measure atmospheric neutrino oscillations. The standard three neutrino mixing scenario can be tested by searching for an additional light sterile neutrino state, which does not interact via the standard weak interaction, but mixes with the three active neutrino states. This leads to an impact on the atmospheric neutrino oscillations below 100 GeV. We present improved limits to the sterile mixing element |U τ4|2 using three years of the DeepCore data taken during 2011-2013.

Atmospheric neutrino oscillation analysis with external constraints in Super-Kamiokande I-IV

NASA Astrophysics Data System (ADS)

Abe, K.; Bronner, C.; Haga, Y.; Hayato, Y.; Ikeda, M.; Iyogi, K.; Kameda, J.; Kato, Y.; Kishimoto, Y.; Marti, Ll.; Miura, M.; Moriyama, S.; Nakahata, M.; Nakajima, T.; Nakano, Y.; Nakayama, S.; Okajima, Y.; Orii, A.; Pronost, G.; Sekiya, H.; Shiozawa, M.; Sonoda, Y.; Takeda, A.; Takenaka, A.; Tanaka, H.; Tasaka, S.; Tomura, T.; Akutsu, R.; Irvine, T.; Kajita, T.; Kametani, I.; Kaneyuki, K.; Nishimura, Y.; Okumura, K.; Richard, E.; Tsui, K. M.; Labarga, L.; Fernandez, P.; Blaszczyk, F. d. M.; Gustafson, J.; Kachulis, C.; Kearns, E.; Raaf, J. L.; Stone, J. L.; Sulak, L. R.; Berkman, S.; Tobayama, S.; Goldhaber, M.; Carminati, G.; Elnimr, M.; Kropp, W. R.; Mine, S.; Locke, S.; Renshaw, A.; Smy, M. B.; Sobel, H. W.; Takhistov, V.; Weatherly, P.; Ganezer, K. S.; Hartfiel, B. L.; Hill, J.; Hong, N.; Kim, J. Y.; Lim, I. T.; Park, R. G.; Akiri, T.; Himmel, A.; Li, Z.; O'Sullivan, E.; Scholberg, K.; Walter, C. W.; Wongjirad, T.; Ishizuka, T.; Nakamura, T.; Jang, J. S.; Choi, K.; Learned, J. G.; Matsuno, S.; Smith, S. N.; Amey, J.; Litchfield, R. P.; Ma, W. Y.; Uchida, Y.; Wascko, M. O.; Cao, S.; Friend, M.; Hasegawa, T.; Ishida, T.; Ishii, T.; Kobayashi, T.; Nakadaira, T.; Nakamura, K.; Oyama, Y.; Sakashita, K.; Sekiguchi, T.; Tsukamoto, T.; Abe, KE.; Hasegawa, M.; Suzuki, A. T.; Takeuchi, Y.; Yano, T.; Hayashino, T.; Hirota, S.; Huang, K.; Ieki, K.; Jiang, M.; Kikawa, T.; Nakamura, KE.; Nakaya, T.; Patel, N. D.; Suzuki, K.; Takahashi, S.; Wendell, R. A.; Anthony, L. H. V.; McCauley, N.; Pritchard, A.; Fukuda, Y.; Itow, Y.; Mitsuka, G.; Murase, M.; Muto, F.; Suzuki, T.; Mijakowski, P.; Frankiewicz, K.; Hignight, J.; Imber, J.; Jung, C. K.; Li, X.; Palomino, J. L.; Santucci, G.; Vilela, C.; Wilking, M. J.; Yanagisawa, C.; Ito, S.; Fukuda, D.; Ishino, H.; Kayano, T.; Kibayashi, A.; Koshio, Y.; Mori, T.; Nagata, H.; Sakuda, M.; Xu, C.; Kuno, Y.; Wark, D.; Di Lodovico, F.; Richards, B.; Tacik, R.; Kim, S. B.; Cole, A.; Thompson, L.; Okazawa, H.; Choi, Y.; Ito, K.; Nishijima, K.; Koshiba, M.; Totsuka, Y.; Suda, Y.; Yokoyama, M.; Calland, R. G.; Hartz, M.; Martens, K.; Quilain, B.; Simpson, C.; Suzuki, Y.; Vagins, M. R.; Hamabe, D.; Kuze, M.; Yoshida, T.; Ishitsuka, M.; Martin, J. F.; Nantais, C. M.; de Perio, P.; Tanaka, H. A.; Konaka, A.; Chen, S.; Wan, L.; Zhang, Y.; Wilkes, R. J.; Minamino, A.; Super-Kamiokande Collaboration

2018-04-01

An analysis of atmospheric neutrino data from all four run periods of Super-Kamiokande optimized for sensitivity to the neutrino mass hierarchy is presented. Confidence intervals for Δ m322 , sin2θ23, sin2θ13 and δC P are presented for normal neutrino mass hierarchy and inverted neutrino mass hierarchy hypotheses, based on atmospheric neutrino data alone. Additional constraints from reactor data on θ13 and from published binned T2K data on muon neutrino disappearance and electron neutrino appearance are added to the atmospheric neutrino fit to give enhanced constraints on the above parameters. Over the range of parameters allowed at 90% confidence level, the normal mass hierarchy is favored by between 91.9% and 94.5% based on the combined Super-Kamiokande plus T2K result.

Constraints on the neutrino flux in NOvA using the near detector data

DOE PAGES

Maan, Kuldeep K.

2016-12-19

NOvA, a long-baseline neutrino oscillation experiment at Fermilab, is designed to measure electron-neutrino appearance and muon-neutrino disappearance in the NuMI beam. NOvA comprises of two finely segmented liquid scintillator detectors at 14 mrad off-axis in the NuMI beam. An accurate prediction of the neutrino flux is needed for precision oscillation and cross-section measurements. Data from the hadron-production experiments and, importantly, from the NOvA Near Detector provide powerful constraints on the muon-neutrino and electron-neutrino fluxes. In particular, the measurement of the neutrino-electron elastic scattering provides an in situ constraint on the absolute flux. Lastly, this poster presents the data-driven predictions ofmore » the NOvA muonneutrino and electron-neutrino flux, and outlines future improvements in the flux determination.« less

Sterile neutrinos and indirect dark matter searches in IceCube

NASA Astrophysics Data System (ADS)

Argüelles, Carlos A.; Kopp, Joachim

2012-07-01

If light sterile neutrinos exist and mix with the active neutrino flavors, this mixing will affect the propagation of high-energy neutrinos from dark matter annihilation in the Sun. In particular, new Mikheyev-Smirnov-Wolfenstein resonances can occur, leading to almost complete conversion of some active neutrino flavors into sterile states. We demonstrate how this can weaken IceCube limits on neutrino capture and annihilation in the Sun and how potential future conflicts between IceCube constraints and direct detection or collider data might be resolved by invoking sterile neutrinos. We also point out that, if the dark matter-nucleon scattering cross section and the allowed annihilation channels are precisely measured in direct detection and collider experiments in the future, IceCube can be used to constrain sterile neutrino models using neutrinos from the dark matter annihilation.

Alzheimer's disease pathological lesions activate the spleen tyrosine kinase.

PubMed

Schweig, Jonas Elias; Yao, Hailan; Beaulieu-Abdelahad, David; Ait-Ghezala, Ghania; Mouzon, Benoit; Crawford, Fiona; Mullan, Michael; Paris, Daniel

2017-09-06

The pathology of Alzheimer's disease (AD) is characterized by dystrophic neurites (DNs) surrounding extracellular Aβ-plaques, microgliosis, astrogliosis, intraneuronal tau hyperphosphorylation and aggregation. We have previously shown that inhibition of the spleen tyrosine kinase (Syk) lowers Aβ production and tau hyperphosphorylation in vitro and in vivo. Here, we demonstrate that Aβ-overexpressing Tg PS1/APPsw, Tg APPsw mice, and tau overexpressing Tg Tau P301S mice exhibit a pathological activation of Syk compared to wild-type littermates. Syk activation is occurring in a subset of microglia and is age-dependently increased in Aβ-plaque-associated dystrophic neurites of Tg PS1/APPsw and Tg APPsw mice. In Tg Tau P301S mice, a pure model of tauopathy, activated Syk occurs in neurons that show an accumulation of misfolded and hyperphosphorylated tau in the cortex and hippocampus. Interestingly, the tau pathology is exacerbated in neurons that display high levels of Syk activation supporting a role of Syk in the formation of tau pathological species in vivo. Importantly, human AD brain sections show both pathological Syk activation in DNs around Aβ deposits and in neurons immunopositive for pathological tau species recapitulating the data obtained in transgenic mouse models of AD. Additionally, we show that Syk overexpression leads to increased tau accumulation and promotes tau hyperphosphorylation at multiple epitopes in human neuron-like SH-SY5Y cells, further supporting a role of Syk in the formation of tau pathogenic species. Collectively, our data show that Syk activation occurs following Aβ deposition and the formation of tau pathological species. Given that we have previously shown that Syk activation also promotes Aβ formation and tau hyperphosphorylation, our data suggest that AD pathological lesions may be self-propagating via a Syk dependent mechanism highlighting Syk as an attractive therapeutic target for the treatment of AD.

Bacterial co-expression of human Tau protein with protein kinase A and 14-3-3 for studies of 14-3-3/phospho-Tau interaction

PubMed Central

Tugaeva, Kristina V.; Tsvetkov, Philipp O.

2017-01-01

Abundant regulatory 14-3-3 proteins have an extremely wide interactome and coordinate multiple cellular events via interaction with specifically phosphorylated partner proteins. Notwithstanding the key role of 14-3-3/phosphotarget interactions in many physiological and pathological processes, they are dramatically underexplored. Here, we focused on the 14-3-3 interaction with human Tau protein associated with the development of several neurodegenerative disorders, including Alzheimer’s and Parkinson’s diseases. Among many known phosphorylation sites within Tau, protein kinase A (PKA) phosphorylates several key residues of Tau and induces its tight interaction with 14-3-3 proteins. However, the stoichiometry and mechanism of 14-3-3 interaction with phosphorylated Tau (pTau) are not clearly elucidated. In this work, we describe a simple bacterial co-expression system aimed to facilitate biochemical and structural studies on the 14-3-3/pTau interaction. We show that dual co-expression of human fetal Tau with PKA in Escherichia coli results in multisite Tau phosphorylation including also naturally occurring sites which were not previously considered in the context of 14-3-3 binding. Tau protein co-expressed with PKA displays tight functional interaction with 14-3-3 isoforms of a different type. Upon triple co-expression with 14-3-3 and PKA, Tau protein could be co-purified with 14-3-3 and demonstrates complex which is similar to that formed in vitro between individual 14-3-3 and pTau obtained from dual co-expression. Although used in this study for the specific case of the previously known 14-3-3/pTau interaction, our co-expression system may be useful to study of other selected 14-3-3/phosphotarget interactions and for validations of 14-3-3 complexes identified by other methods. PMID:28575131

Age-Related Differences in Diagnostic Accuracy of Plasma GFAP and Tau For Identifying Acute Intracranial Trauma on CT: A TRACK-TBI Study.

PubMed

Gardner, Raquel C; Rubenstein, Richard; Wang, Kevin K W; Korley, Frederick Kofi; Yue, John K; Yuh, Esther Lim; Mukherjee, Pratik; Valadka, Alex; Okonkwo, David O; Diaz-Arrastia, Ramon; Manley, Geoffrey

2018-05-02

Plasma tau and glial fibrillary acidic protein (GFAP) are promising biomarkers for identifying traumatic brain injury (TBI) patients with intracranial trauma on CT. Accuracy in older adults with mild TBI (mTBI), the fastest growing TBI population, is unknown. Our aim was to assess for age-related differences in diagnostic accuracy of plasma tau and GFAP for identifying intracranial trauma on CT. Samples from 169 patients (age <40y [n=79], age 40-59y [n=60], age 60y+ [n=30]), a subset of patients from the TRACK-TBI Pilot study, who presented with mTBI (GCS 13-15), received head CT, and consented to blood-draw within 24h of injury were assayed for hyperphosphorylated-tau (P-tau), total-tau (T-tau; both via amplification-linked enhanced immunoassay using multi-arrayed fiberoptics), and GFAP (via sandwich enzyme-linked immunosorbent assay). P-tau, T-tau, P-tau:T-tau ratio, and GFAP concentration were significantly associated with CT findings. Overall, discriminative ability declined with increasing age for all assays, but this decline was only statistically significant for GFAP (area under the receiver operating characteristic curve [AUC]: old 0.73[ref] vs. young 0.93[p=0.037] or middle-aged 0.92[p<0.050]). P-tau concentration showed consistently highest diagnostic accuracy across all age-groups (AUC: old 0.84[ref] vs. young 0.95[p=0.274] or middle-aged 0.93[p=0.367]). Comparison of models including P-tau alone versus P-tau plus GFAP revealed significant added value of GFAP. In conclusion, the GFAP assay was less accurate for identifying intracranial trauma on CT among older versus younger mTBI patients. Mechanisms of this age-related difference, including role of assay methodology, specific TBI neuroanatomy, pre-existing conditions, and anti-thrombotic use warrant further study.

Taurine Bromamine: Reactivity of an Endogenous and Exogenous Anti-Inflammatory and Antimicrobial Amino Acid Derivative

PubMed Central

Bertozo, Luiza De Carvalho; Morgon, Nelson Henrique; De Souza, Aguinaldo Robinson; Ximenes, Valdecir Farias

2016-01-01

Taurine bromamine (Tau-NHBr) is produced by the reaction between hypobromous acid (HOBr) and the amino acid taurine. There are increasing number of applications of Tau-NHBr as an anti-inflammatory and microbicidal drug for topical usage. Here, we performed a comprehensive study of the chemical reactivity of Tau-NHBr with endogenous and non-endogenous compounds. Tau-NHBr reactivity was compared with HOBr, hypochlorous acid (HOCl) and taurine chloramine (Tau-NHCl). The second-order rate constants (k2) for the reactions between Tau-NHBr and tryptophan (7.7 × 102 M−1s−1), melatonin (7.3 × 103 M−1s−1), serotonin (2.9 × 103 M−1s−1), dansylglycine (9.5 × 101 M−1s−1), tetramethylbenzidine (6.4 × 102 M−1s−1) and H2O2 (3.9 × M−1s−1) were obtained. Tau-NHBr demonstrated the following selectivity regarding its reactivity with free amino acids: tryptophan > cysteine ~ methionine > tyrosine. The reactivity of Tau-NHBr was strongly affected by the pH of the medium (for instance with dansylglycine: pH 5.0, 1.1 × 104 M−1s−1, pH 7.0, 9.5 × 10 M−1s−1 and pH 9.0, 1.7 × 10 M−1s−1), a property that is related to the formation of the dibromamine form at acidic pH (Tau-NBr2). The formation of singlet oxygen was observed in the reaction between Tau-NHBr and H2O2. Tau-NHBr was also able to react with linoleic acid, but with low efficiency compared with HOBr and HOCl. Compared with HOBr, Tau-NHBr was not able to react with nucleosides. In conclusion, the following reactivity sequence was established: HOBr > HOCl > Tau-NHBr > Tau-NHCl. These findings can be very helpful for researchers interested in biological applications of taurine haloamines. PMID:27110829

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aartsen, M. G.; Ackermann, M.; Adams, J.

We present an all-sky search for muon neutrinos produced during the prompt γ -ray emission of 1172 gamma-ray bursts (GRBs) with the IceCube Neutrino Observatory. The detection of these neutrinos would constitute evidence for ultra-high-energy cosmic-ray (UHECR) production in GRBs, as interactions between accelerated protons and the prompt γ -ray field would yield charged pions, which decay to neutrinos. A previously reported search for muon neutrino tracks from northern hemisphere GRBs has been extended to include three additional years of IceCube data. A search for such tracks from southern hemisphere GRBs in five years of IceCube data has been introducedmore » to enhance our sensitivity to the highest energy neutrinos. No significant correlation between neutrino events and observed GRBs is seen in the new data. Combining this result with previous muon neutrino track searches and a search for cascade signature events from all neutrino flavors, we obtain new constraints for single-zone fireball models of GRB neutrino and UHECR production.« less

Effects of sterile neutrino and extra-dimension on big bang nucleosynthesis

NASA Astrophysics Data System (ADS)

Jang, Dukjae; Kusakabe, Motohiko; Cheoun, Myung-Ki

2018-04-01

We study effects of the sterile neutrino in the five-dimensional universe on the big bang nucleosynthesis (BBN). Since the five-dimensional universe model leads to an additional term in the Friedmann equation and the energy density of the sterile neutrino increases the total energy density, this model can affect the primordial abundance via changing the cosmic expansion rate. The energy density of the sterile neutrino can be determined by a rate equation for production of the sterile neutrino. We show that not only the mixing angle and the mass of the sterile neutrino, but also a resonant effect in the oscillation between sterile and active neutrinos is important to determine a relic abundance of the sterile neutrino. In this study, we also investigate how the sterile neutrino in extra-dimensional model can affect the BBN, and constrain the parameters related to the above properties of the sterile neutrino by using the observational primordial abundances of light elements.

Neutrino astronomy at the South Pole: Latest results from the IceCube neutrino observatory and its future development

NASA Astrophysics Data System (ADS)

Toscano, S.; IceCube Collaboration

2017-12-01

The IceCube Neutrino Observatory is a cubic-kilometer neutrino telescope located at the geographic South Pole. Buried deep under the Antarctic ice sheet, an array of 5160 Digital Optical Modules (DOMs) is used to capture the Cherenkov light emitted by relativistic particles generated from neutrino interactions. The main goal of IceCube is the detection of astrophysical neutrinos. In 2013 the IceCube neutrino telescope discovered a high-energy diffuse flux of neutrino events with energy ranging from tens of TeV up to few PeV of cosmic origin. Meanwhile, different analyses confirm the discovery and search for possible correlations with astrophysical sources. However, the source of these neutrinos remains a mystery, since no counterparts have been identified yet. In this contribution we give an overview of the detection principles of IceCube, the most recent results, and the plans for a next-generation neutrino detector, dubbed IceCube-Gen2.

Measurement of Neutrino Oscillation Parameters from Muon Neutrino Disappearance with an Off-Axis Beam

NASA Astrophysics Data System (ADS)

Abe, K.; Adam, J.; Aihara, H.; Akiri, T.; Andreopoulos, C.; Aoki, S.; Ariga, A.; Ariga, T.; Assylbekov, S.; Autiero, D.; Barbi, M.; Barker, G. J.; Barr, G.; Bass, M.; Batkiewicz, M.; Bay, F.; Bentham, S. W.; Berardi, V.; Berger, B. E.; Berkman, S.; Bertram, I.; Bhadra, S.; Blaszczyk, F. d. M.; Blondel, A.; Bojechko, C.; Bordoni, S.; Boyd, S. B.; Brailsford, D.; Bravar, A.; Bronner, C.; Buchanan, N.; Calland, R. G.; Caravaca Rodríguez, J.; Cartwright, S. L.; Castillo, R.; Catanesi, M. G.; Cervera, A.; Cherdack, D.; Christodoulou, G.; Clifton, A.; Coleman, J.; Coleman, S. J.; Collazuol, G.; Connolly, K.; Cremonesi, L.; Curioni, A.; Dabrowska, A.; Danko, I.; Das, R.; Davis, S.; de Perio, P.; De Rosa, G.; Dealtry, T.; Dennis, S. R.; Densham, C.; Di Lodovico, F.; Di Luise, S.; Drapier, O.; Duboyski, T.; Duffy, K.; Dufour, F.; Dumarchez, J.; Dytman, S.; Dziewiecki, M.; Emery, S.; Ereditato, A.; Escudero, L.; Finch, A. J.; Frank, E.; Friend, M.; Fujii, Y.; Fukuda, Y.; Furmanski, A. P.; Galymov, V.; Gaudin, A.; Giffin, S.; Giganti, C.; Gilje, K.; Golan, T.; Gomez-Cadenas, J. J.; Gonin, M.; Grant, N.; Gudin, D.; Hadley, D. R.; Haesler, A.; Haigh, M. D.; Hamilton, P.; Hansen, D.; Hara, T.; Hartz, M.; Hasegawa, T.; Hastings, N. C.; Hayato, Y.; Hearty, C.; Helmer, R. L.; Hierholzer, M.; Hignight, J.; Hillairet, A.; Himmel, A.; Hiraki, T.; Hirota, S.; Holeczek, J.; Horikawa, S.; Huang, K.; Ichikawa, A. K.; Ieki, K.; Ieva, M.; Ikeda, M.; Imber, J.; Insler, J.; Irvine, T. J.; Ishida, T.; Ishii, T.; Ives, S. J.; Iyogi, K.; Izmaylov, A.; Jacob, A.; Jamieson, B.; Johnson, R. A.; Jo, J. H.; Jonsson, P.; Joo, K. K.; Jung, C. K.; Kaboth, A. C.; Kajita, T.; Kakuno, H.; Kameda, J.; Kanazawa, Y.; Karlen, D.; Karpikov, I.; Kearns, E.; Khabibullin, M.; Khotjantsev, A.; Kielczewska, D.; Kikawa, T.; Kilinski, A.; Kim, J.; Kim, S. B.; Kisiel, J.; Kitching, P.; Kobayashi, T.; Kogan, G.; Kolaceke, A.; Konaka, A.; Kormos, L. L.; Korzenev, A.; Koseki, K.; Koshio, Y.; Kreslo, I.; Kropp, W.; Kubo, H.; Kudenko, Y.; Kumaratunga, S.; Kurjata, R.; Kutter, T.; Lagoda, J.; Laihem, K.; Laveder, M.; Lawe, M.; Lazos, M.; Lee, K. P.; Licciardi, C.; Lim, I. T.; Lindner, T.; Lister, C.; Litchfield, R. P.; Longhin, A.; Lopez, G. D.; Ludovici, L.; Macaire, M.; Magaletti, L.; Mahn, K.; Malek, M.; Manly, S.; Marino, A. D.; Marteau, J.; Martin, J. F.; Maruyama, T.; Marzec, J.; Masliah, P.; Mathie, E. L.; Matveev, V.; Mavrokoridis, K.; Mazzucato, E.; McCarthy, M.; McCauley, N.; McFarland, K. S.; McGrew, C.; Metelko, C.; Mijakowski, P.; Miller, C. A.; Minamino, A.; Mineev, O.; Mine, S.; Missert, A.; Miura, M.; Monfregola, L.; Moriyama, S.; Mueller, Th. A.; Murakami, A.; Murdoch, M.; Murphy, S.; Myslik, J.; Nagasaki, T.; Nakadaira, T.; Nakahata, M.; Nakai, T.; Nakamura, K.; Nakayama, S.; Nakaya, T.; Nakayoshi, K.; Naples, D.; Nielsen, C.; Nirkko, M.; Nishikawa, K.; Nishimura, Y.; O'Keeffe, H. M.; Ohta, R.; Okumura, K.; Okusawa, T.; Oryszczak, W.; Oser, S. M.; Otani, M.; Owen, R. A.; Oyama, Y.; Pac, M. Y.; Palladino, V.; Paolone, V.; Payne, D.; Pearce, G. F.; Perevozchikov, O.; Perkin, J. D.; Petrov, Y.; Pinzon Guerra, E. S.; Pistillo, C.; Plonski, P.; Poplawska, E.; Popov, B.; Posiadala, M.; Poutissou, J.-M.; Poutissou, R.; Przewlocki, P.; Quilain, B.; Radicioni, E.; Ratoff, P. N.; Ravonel, M.; Rayner, M. A. M.; Redij, A.; Reeves, M.; Reinherz-Aronis, E.; Retiere, F.; Robert, A.; Rodrigues, P. A.; Rondio, E.; Roth, S.; Rubbia, A.; Ruterbories, D.; Sacco, R.; Sakashita, K.; Sánchez, F.; Sato, F.; Scantamburlo, E.; Scholberg, K.; Schwehr, J.; Scott, M.; Seiya, Y.; Sekiguchi, T.; Sekiya, H.; Sgalaberna, D.; Shiozawa, M.; Short, S.; Shustrov, Y.; Sinclair, P.; Smith, B.; Smith, R. J.; Smy, M.; Sobczyk, J. T.; Sobel, H.; Sorel, M.; Southwell, L.; Stamoulis, P.; Steinmann, J.; Still, B.; Suda, Y.; Suzuki, A.; Suzuki, K.; Suzuki, S. Y.; Suzuki, Y.; Szeglowski, T.; Tacik, R.; Tada, M.; Takahashi, S.; Takeda, A.; Takeuchi, Y.; Tanaka, H. K.; Tanaka, H. A.; Tanaka, M. M.; Taylor, I. J.; Terhorst, D.; Terri, R.; Thompson, L. F.; Thorley, A.; Tobayama, S.; Toki, W.; Tomura, T.; Totsuka, Y.; Touramanis, C.; Tsukamoto, T.; Tzanov, M.; Uchida, Y.; Ueno, K.; Vacheret, A.; Vagins, M.; Vasseur, G.; Wachala, T.; Waldron, A. V.; Walter, C. W.; Wark, D.; Wascko, M. O.; Weber, A.; Wendell, R.; Wilkes, R. J.; Wilking, M. J.; Wilkinson, C.; Williamson, Z.; Wilson, J. R.; Wilson, R. J.; Wongjirad, T.; Yamada, Y.; Yamamoto, K.; Yanagisawa, C.; Yen, S.; Yershov, N.; Yokoyama, M.; Yuan, T.; Zalewska, A.; Zalipska, J.; Zambelli, L.; Zaremba, K.; Ziembicki, M.; Zimmerman, E. D.; Zito, M.; Żmuda, J.

2013-11-01

The T2K Collaboration reports a precision measurement of muon neutrino disappearance with an off-axis neutrino beam with a peak energy of 0.6 GeV. Near detector measurements are used to constrain the neutrino flux and cross section parameters. The Super-Kamiokande far detector, which is 295 km downstream of the neutrino production target, collected data corresponding to 3.01×1020 protons on target. In the absence of neutrino oscillations, 205±17 (syst) events are expected to be detected while only 58 muon neutrino event candidates are observed. A fit to the neutrino rate and energy spectrum, assuming three neutrino flavors and normal mass hierarchy yields a best-fit mixing angle sin⁡2(θ23)=0.514±0.082 and mass splitting |Δm322|=2.44-0.15+0.17×10-3eV2/c4. Our result corresponds to the maximal oscillation disappearance probability.

Seed-competent HMW tau species accumulates in the cerebrospinal fluid of Alzheimer's disease mouse model and human patients

PubMed Central

Takeda, Shuko; Commins, Caitlin; DeVos, Sarah L.; Nobuhara, Chloe K.; Wegmann, Susanne; Roe, Allyson D.; Costantino, Isabel; Fan, Zhanyun; Nicholls, Samantha B.; Sherman, Alexis E.; Trisini Lipsanopoulos, Ana T.; Scherzer, Clemens R.; Carlson, George A.; Pitstick, Rose; Peskind, Elaine R.; Raskind, Murray A.; Li, Ge; Montine, Thomas J.; Frosch, Matthew P.; Hyman, Bradley T.

2016-01-01

Objective Cerebrospinal fluid (CSF) tau is an excellent surrogate marker for assessing neuropathological changes that occur in Alzheimer's disease (AD) patients. However, whether the elevated tau in AD CSF is just a marker of neurodegeneration or in fact a part of the disease process is uncertain. Moreover, it is unknown how CSF tau relates to the recently described soluble high-molecular-weight (HMW) species that is found in postmortem AD brain and can be taken up by neurons and seed aggregates. Methods We have examined seeding and uptake properties of brain extracellular tau from various sources including: interstitial fluid (ISF) and CSF from an AD transgenic mouse model, and postmortem ventricular and antemortem lumbar CSF from AD patients. Results We found that brain ISF and CSF tau from the AD mouse model can be taken up by cells and induce intracellular aggregates. Ventricular CSF from AD patients contained a rare HMW tau species that exerted a higher seeding activity. Notably, the HMW tau species was also detected in lumbar CSF from AD patients and its levels were significantly elevated compared with control subjects. HMW tau derived from CSF of AD patients was seed-competent in vitro. Interpretation These findings suggest that CSF from an AD brain contains potentially bioactive HMW tau species giving new insights into the role of CSF tau and biomarker development for AD. PMID:27351289

Plasma tau in Alzheimer disease.

PubMed

Mattsson, Niklas; Zetterberg, Henrik; Janelidze, Shorena; Insel, Philip S; Andreasson, Ulf; Stomrud, Erik; Palmqvist, Sebastian; Baker, David; Tan Hehir, Cristina A; Jeromin, Andreas; Hanlon, David; Song, Linan; Shaw, Leslie M; Trojanowski, John Q; Weiner, Michael W; Hansson, Oskar; Blennow, Kaj

2016-10-25

To test whether plasma tau is altered in Alzheimer disease (AD) and whether it is related to changes in cognition, CSF biomarkers of AD pathology (including β-amyloid [Aβ] and tau), brain atrophy, and brain metabolism. This was a study of plasma tau in prospectively followed patients with AD (n = 179), patients with mild cognitive impairment (n = 195), and cognitive healthy controls (n = 189) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and cross-sectionally studied patients with AD (n = 61), mild cognitive impairment (n = 212), and subjective cognitive decline (n = 174) and controls (n = 274) from the Biomarkers for Identifying Neurodegenerative Disorders Early and Reliably (BioFINDER) study at Lund University, Sweden. A total of 1284 participants were studied. Associations were tested between plasma tau and diagnosis, CSF biomarkers, MRI measures, 18 fluorodeoxyglucose-PET, and cognition. Higher plasma tau was associated with AD dementia, higher CSF tau, and lower CSF Aβ 42 , but the correlations were weak and differed between ADNI and BioFINDER. Longitudinal analysis in ADNI showed significant associations between plasma tau and worse cognition, more atrophy, and more hypometabolism during follow-up. Plasma tau partly reflects AD pathology, but the overlap between normal aging and AD is large, especially in patients without dementia. Despite group-level differences, these results do not support plasma tau as an AD biomarker in individual people. Future studies may test longitudinal plasma tau measurements in AD. © 2016 American Academy of Neurology.

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

PubMed Central

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

2016-01-01

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

α-Synuclein Fibrils Exhibit Gain of Toxic Function, Promoting Tau Aggregation and Inhibiting Microtubule Assembly*

PubMed Central

Oikawa, Takayuki; Nonaka, Takashi; Terada, Makoto; Tamaoka, Akira; Hisanaga, Shin-ichi; Hasegawa, Masato

2016-01-01

α-Synuclein is the major component of Lewy bodies and Lewy neurites in Parkinson disease and dementia with Lewy bodies and of glial cytoplasmic inclusions in multiple system atrophy. It has been suggested that α-synuclein fibrils or intermediate protofibrils in the process of fibril formation may have a toxic effect on neuronal cells. In this study, we investigated the ability of soluble monomeric α-synuclein to promote microtubule assembly and the effects of conformational changes of α-synuclein on Tau-promoted microtubule assembly. In marked contrast to previous findings, monomeric α-synuclein had no effect on microtubule polymerization. However, both α-synuclein fibrils and protofibrils inhibited Tau-promoted microtubule assembly. The inhibitory effect of α-synuclein fibrils was greater than that of the protofibrils. Dot blot overlay assay and spin-down techniques revealed that α-synuclein fibrils bind to Tau and inhibit microtubule assembly by depleting the Tau available for microtubule polymerization. Using various deletion mutants of α-synuclein and Tau, the acidic C-terminal region of α-synuclein and the basic central region of Tau were identified as regions involved in the binding. Furthermore, introduction of α-synuclein fibrils into cultured cells overexpressing Tau protein induced Tau aggregation. These results raise the possibility that α-synuclein fibrils interact with Tau, inhibit its function to stabilize microtubules, and also promote Tau aggregation, leading to dysfunction of neuronal cells. PMID:27226637

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. © 2016 American Association of Neuropathologists, Inc. All rights reserved.

No support for premature central nervous system aging in HIV-1 when measured by cerebrospinal fluid phosphorylated tau (p-tau).

PubMed

Krut, Jan J; Price, Richard W; Zetterberg, Henrik; Fuchs, Dietmar; Hagberg, Lars; Yilmaz, Aylin; Cinque, Paola; Nilsson, Staffan; Gisslén, Magnus

2017-07-04

The prevalence of neurocognitive deficits are reported to be high in HIV-1 positive patients, even with suppressive antiretroviral treatment, and it has been suggested that HIV can cause accelerated aging of the brain. In this study we measured phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) as a potential marker for premature central nervous system (CNS) aging. P-tau increases with normal aging but is not affected by HIV-associated neurocognitive disorders. With a cross-sectional retrospective design, p-tau, total tau (t-tau), neopterin and HIV-RNA were measured in CSF together with plasma HIV-RNA and blood CD4 + T-cells of 225 HIV-infected patients <50 y of age, subdivided into 3 groups: untreated neuroasymptomatic (NA) (n = 145), on suppressive antiretroviral treatment (cART) (n = 49), and HIV-associated dementia (HAD) (n = 31). HIV-negative healthy subjects served as controls (n = 79). P-tau was not significantly higher in any HIV-infected group compared to HIV-negative controls. Significant increases in t-tau were found as expected in patients with HAD compared to NA, cART, and control groups (p < 0.001 ). P-tau was not higher in HIV-infected patients compared to uninfected controls, thus failing to support a role for premature or accelerated brain aging in HIV infection.

Light sterile neutrinos and neutrinoless double-beta decay

NASA Astrophysics Data System (ADS)

Giunti, Carlo

2017-10-01

The LSND, Gallium and reactor neutrino anomalies can be explained by short-baseline neutrino oscillations due to the mixing of the active neutrinos with sterile neutrinos at the eV scale. I review the results of a 3+1 global fit of short-baseline neutrino oscillation data that includes the recent measurements of the MINOS, IceCube, and NEOS experiments, and I discuss the implications for neutrinoless double-beta decay.

Invited review article: IceCube: an instrument for neutrino astronomy.

PubMed

Halzen, Francis; Klein, Spencer R

2010-08-01

Neutrino astronomy beyond the Sun was first imagined in the late 1950s; by the 1970s, it was realized that kilometer-scale neutrino detectors were required. The first such instrument, IceCube, is near completion and taking data. The IceCube project transforms 1 km(3) of deep and ultratransparent Antarctic ice into a particle detector. A total of 5160 optical sensors is embedded into a gigaton of Antarctic ice to detect the Cherenkov light emitted by secondary particles produced when neutrinos interact with nuclei in the ice. Each optical sensor is a complete data acquisition system including a phototube, digitization electronics, control and trigger systems, and light-emitting diodes for calibration. The light patterns reveal the type (flavor) of neutrino interaction and the energy and direction of the neutrino, making neutrino astronomy possible. The scientific missions of IceCube include such varied tasks as the search for sources of cosmic rays, the observation of galactic supernova explosions, the search for dark matter, and the study of the neutrinos themselves. These reach energies well beyond those produced with accelerator beams. The outline of this review is as follows: neutrino astronomy and kilometer-scale detectors, high-energy neutrino telescopes: methodologies of neutrino detection, IceCube hardware, high-energy neutrino telescopes: beyond astronomy, and future projects.

SHEDDING NEW LIGHT ON EXPLODING STARS: TERASCALE SIMULATIONS OF NEUTRINO-DRIVEN SUPERNOVAE AND THEIR NUCLEOSYNTHESIS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haxton, Wick

2012-03-07

This project was focused on simulations of core-collapse supernovae on parallel platforms. The intent was to address a number of linked issues: the treatment of hydrodynamics and neutrino diffusion in two and three dimensions; the treatment of the underlying nuclear microphysics that governs neutrino transport and neutrino energy deposition; the understanding of the associated nucleosynthesis, including the r-process and neutrino process; the investigation of the consequences of new neutrino phenomena, such as oscillations; and the characterization of the neutrino signal that might be recorded in terrestrial detectors. This was a collaborative effort with Oak Ridge National Laboratory, State University ofmore » New York at Stony Brook, University of Illinois at Urbana-Champaign, University of California at San Diego, University of Tennessee at Knoxville, Florida Atlantic University, North Carolina State University, and Clemson. The collaborations tie together experts in hydrodynamics, nuclear physics, computer science, and neutrino physics. The University of Washington contributions to this effort include the further development of techniques to solve the Bloch-Horowitz equation for effective interactions and operators; collaborative efforts on developing a parallel Lanczos code; investigating the nuclear and neutrino physics governing the r-process and neutrino physics; and exploring the effects of new neutrino physics on the explosion mechanism, nucleosynthesis, and terrestrial supernova neutrino detection.« less

Detection of Supernova Neutrinos on the Earth for Large θ13

NASA Astrophysics Data System (ADS)

Xu, Jing; Huang, Ming-Yang; Hu, Li-Jun; Guo, Xin-Heng; Young, Bing-Lin

2014-02-01

Supernova (SN) neutrinos detected on the Earth are subject to the shock wave effects, the Mikheyev—Smirnov—Wolfenstein (MSW) effects, the neutrino collective effects and the Earth matter effects. Considering the recent experimental result about the large mixing angle θ13 (≃ 8.8°) provided by the Daya Bay Collaboration and applying the available knowledge for the neutrino conversion probability in the high resonance region of SN, PH, which is in the form of hypergeometric function in the case of large θ13, we deduce the expression of PH taking into account the shock wave effects. It is found that PH is not zero in a certain range of time due to the shock wave effects. After considering all the four physical effects and scanning relevant parameters, we calculate the event numbers of SN neutrinos for the “Garching” distribution of neutrino energy spectrum. From the numerical results, it is found that the behaviors of neutrino event numbers detected on the Earth depend on the neutrino mass hierarchy and neutrino spectrum parameters including the dimensionless pinching parameter βα (where α refers to neutrino flavor), the average energy , and the SN neutrino luminosities Lα. Finally, we give the ranges of SN neutrino event numbers that will be detected at the Daya Bay experiment.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aaboud, M.; Aad, G.; Abbott, B.

Here, a search for heavy neutral Higgs bosons and Z' bosons is performed using a data sample corresponding to an integrated luminosity of 36.1 fb –1 from proton-proton collisions at √s=13 TeV recorded by the ATLAS detector at the LHC during 2015 and 2016. The heavy resonance is assumed to decay to τ +τ – with at least one tau lepton decaying to final states with hadrons and a neutrino. The search is performed in the mass range of 0.2-2.25 TeV for Higgs bosons and 0.2-4.0 TeV for Z' bosons. The data are in good agreement with the background predictedmore » by the Standard Model. The results are interpreted in benchmark scenarios. In the context of the hMSSM scenario, the data exclude tan β > 1.0 for m A = 0.25 TeV and tan β > 42 for m A = 1.5 TeV at the 95% confidence level. For the Sequential Standard Model, Z SSM ' with m Z' < 2.42 TeV is excluded at 95% confidence level, while Z NU ' with m Z' < 2.25 TeV is excluded for the non-universal G(221) model that exhibits enhanced couplings to third-generation fermions.« less

RNA Interference Silencing of Glycogen Synthase Kinase 3β Inhibites Tau Phosphorylation in Mice with Alzheimer Disease.

PubMed

Bian, Hong; Bian, Wei; Lin, Xiaoying; Ma, Zhaoyin; Chen, Wen; Pu, Ying

2016-09-01

To explore the effect of glycogen synthase kinase 3β (GSK-3β) silencing on Tau-5 phosphorylation in mice suffering Alzheimer disease (AD). GSK-3β was firstly silenced in human neuroblastoma SH-SY5Y cells using special lentivirus (LV) and the content of Tau (A-12), p-Tau (Ser396) and p-Tau (PHF-6) proteins. GSK-3β was also silenced in APP/PS1 mouse model of AD mice, which were divided into three groups (n = 10): AD, vehicle, and LV group. Ten C57 mice were used as control. The memory ability of mice was tested by square water maze, and the morphological changes of hippocampus and neuron death were analyzed by haematoxylin-eosin staining. Moreover, the levels of Tau and phosphorylated Tau (p-Tau) were detected by western blotting and immunohistochemistry, respectively. The lentivirus-mediated GSK-3β silencing system was successfully developed and silencing GSK-3β at the cellular level reduced Tau phosphorylation obviously. Moreover, GSK-3β silence significantly improved the memory ability of AD mice in LV group compared with AD group (P < 0.05) according to the latency periods and error numbers. As for the hippocampus morphology and neuron death, no significant change was observed between LV group and normal control. Immunohistochemical detection and western blotting revealed that the levels of Tau and p-Tau were significantly down-regulated after GSK-3β silence. Silencing GSK-3β may have a positive effect on inhibiting the pathologic progression of AD through down-regulating the level of p-Tau.

Levels of Nonphosphorylated and Phosphorylated Tau in Cerebrospinal Fluid of Alzheimer’s Disease Patients

PubMed Central

Hu, Yuan Yuan; He, Shan Shu; Wang, Xiaochuan; Duan, Qiu Hong; Grundke-Iqbal, Inge; Iqbal, Khalid; Wang, Jianzhi

2002-01-01

We have developed an ultrasensitive bienzyme-substrate-recycle enzyme-linked immunosorbent assay for the measurement of Alzheimer’s disease (AD) abnormally hyperphosphorylated tau in cerebrospinal fluid (CSF). The assay, which recognizes attomolar amounts of tau, is ∼400 and ∼1300 times more sensitive than conventional enzyme-linked immunosorbent assay in determining the hyperphosphorylated tau and total tau, respectively. With this method, we measured both total tau and tau phosphorylated at Ser-396/Ser-404 in lumbar CSFs from AD and control patients. We found that the total tau was 215 ± 77 pg/ml in cognitively normal control (n = 56), 234 ± 92 pg/ml in non-AD neurological (n = 37), 304 ± 126 pg/ml in vascular dementia (n = 46), and 486 ± 168 pg/ml (n = 52) in AD patients, respectively. However, a remarkably elevated level in phosphorylated tau was only found in AD (187 ± 84 pg/ml), as compared with normal controls (54 ± 33 pg/ml), non-AD (63 ± 34 pg/ml), and vascular dementia (72 ± 33 pg/ml) groups. If we used the ratio of hyperphosphorylated tau to total tau of ≥0.33 as cutoff for AD diagnosis, we could confirm the diagnosis in 96% of the clinically diagnosed patients with a specificity of 95%, 86%, 100%, and 94% against nonneurological, non-AD neurological, vascular dementia, and all of the three control groups combined, respectively. It is suggested that the CSF level of tau phosphorylated at Ser-396/Ser-404 is a promising diagnostic marker of AD. PMID:11943712

Capturing Neutrinos from a Star's Final Hours

NASA Astrophysics Data System (ADS)

Hensley, Kerry

2018-04-01

What happens on the last day of a massive stars life? In the hours before the star collapses and explodes as a supernova, the rapid evolution of material in its core creates swarms of neutrinos. Observing these neutrinos may help us understand the final stages of a massive stars life but theyve never been detected.A view of some of the 1,520 phototubes within the MiniBooNE neutrino detector. Observations from this and other detectors are helping to illuminate the nature of the mysterious neutrino. [Fred Ullrich/FNAL]Silent Signposts of Stellar EvolutionThe nuclear fusion that powers stars generates tremendous amounts of energy. Much of this energy is emitted as photons, but a curious and elusive particle the neutrino carries away most of the energy in the late stages of stellar evolution.Stellar neutrinos can be created through two processes: thermal processesand beta processes. Thermal processes e.g.,pair production, in which a particle/antiparticle pair are created depend on the temperature and pressure of the stellar core. Beta processes i.e.,when a proton converts to a neutron, or vice versa are instead linked to the isotopic makeup of the stars core. This means that, if we can observe them, beta-process neutrinos may be able to tell us about the last steps of stellar nucleosynthesis in a dying star.But observing these neutrinos is not so easilydone. Neutrinos arenearly massless, neutral particles that interact only feebly with matter; out of the whopping 1060neutrinos released in a supernova explosion, even the most sensitive detectors only record the passage of just a few. Do we have a chance of detectingthe beta-process neutrinos that are released in the final few hours of a stars life, beforethe collapse?Neutrino luminosities leading up to core collapse. Shortly before collapse, the luminosity of beta-process neutrinos outshines that of any other neutrino flavor or origin. [Adapted from Patton et al. 2017]Modeling Stellar CoresTo answer this question, Kelly Patton (University of Washington) and collaborators first used a stellar evolution model to explore neutrino production in massive stars. They modeled the evolution of two massive stars 15 and 30 times the mass of our Sun from the onset of nuclear fusion to the moment of collapse.The authors found that in the last few hours before collapse, during which the material in the stars cores is rapidly upcycled into heavier elements, the flux from beta-process neutrinos rivals that of thermal neutrinos and even exceeds it at high energies. So now we know there are many beta-process neutrinos but can we spot them?Neutrino and antineutrino fluxes at Earth from the last 2 hours of a 30-solar-mass stars life compared to the flux from background sources. The rows represent calculations using two different neutrino mass hierarchies. Click to enlarge. [Patton et al. 2017]Observing Elusive NeutrinosFor an imminent supernova at a distance of 1 kiloparsec, the authors find that the presupernova electron neutrino flux rises above the background noise from the Sun, nuclear reactors, and radioactive decay within the Earth in the final two hours before collapse.Based on these calculations, current and future neutrino observatories should be able to detect tens of neutrinos from a supernova within 1 kiloparsec, about 30% of which would be beta-process neutrinos. As the distance to the star increases, the time and energy window within which neutrinos can be observed gradually narrows, until it closes for stars at a distance of about 30 kiloparsecs.Are there any nearby supergiants soon to go supernova so these predictions can be tested? At a distance of only 650 light-years, the red supergiant star Betelgeuse should produce detectable neutrinos when it explodes an exciting opportunity for astronomers in the far future!CitationKelly M. Patton et al 2017ApJ8516. doi:10.3847/1538-4357/aa95c4

Neutrino physics with JUNO

NASA Astrophysics Data System (ADS)

An, Fengpeng; An, Guangpeng; An, Qi; Antonelli, Vito; Baussan, Eric; Beacom, John; Bezrukov, Leonid; Blyth, Simon; Brugnera, Riccardo; Buizza Avanzini, Margherita; Busto, Jose; Cabrera, Anatael; Cai, Hao; Cai, Xiao; Cammi, Antonio; Cao, Guofu; Cao, Jun; Chang, Yun; Chen, Shaomin; Chen, Shenjian; Chen, Yixue; Chiesa, Davide; Clemenza, Massimiliano; Clerbaux, Barbara; Conrad, Janet; D'Angelo, Davide; De Kerret, Hervé; Deng, Zhi; Deng, Ziyan; Ding, Yayun; Djurcic, Zelimir; Dornic, Damien; Dracos, Marcos; Drapier, Olivier; Dusini, Stefano; Dye, Stephen; Enqvist, Timo; Fan, Donghua; Fang, Jian; Favart, Laurent; Ford, Richard; Göger-Neff, Marianne; Gan, Haonan; Garfagnini, Alberto; Giammarchi, Marco; Gonchar, Maxim; Gong, Guanghua; Gong, Hui; Gonin, Michel; Grassi, Marco; Grewing, Christian; Guan, Mengyun; Guarino, Vic; Guo, Gang; Guo, Wanlei; Guo, Xin-Heng; Hagner, Caren; Han, Ran; He, Miao; Heng, Yuekun; Hsiung, Yee; Hu, Jun; Hu, Shouyang; Hu, Tao; Huang, Hanxiong; Huang, Xingtao; Huo, Lei; Ioannisian, Ara; Jeitler, Manfred; Ji, Xiangdong; Jiang, Xiaoshan; Jollet, Cécile; Kang, Li; Karagounis, Michael; Kazarian, Narine; Krumshteyn, Zinovy; Kruth, Andre; Kuusiniemi, Pasi; Lachenmaier, Tobias; Leitner, Rupert; Li, Chao; Li, Jiaxing; Li, Weidong; Li, Weiguo; Li, Xiaomei; Li, Xiaonan; Li, Yi; Li, Yufeng; Li, Zhi-Bing; Liang, Hao; Lin, Guey-Lin; Lin, Tao; Lin, Yen-Hsun; Ling, Jiajie; Lippi, Ivano; Liu, Dawei; Liu, Hongbang; Liu, Hu; Liu, Jianglai; Liu, Jianli; Liu, Jinchang; Liu, Qian; Liu, Shubin; Liu, Shulin; Lombardi, Paolo; Long, Yongbing; Lu, Haoqi; Lu, Jiashu; Lu, Jingbin; Lu, Junguang; Lubsandorzhiev, Bayarto; Ludhova, Livia; Luo, Shu; Lyashuk, Vladimir; Möllenberg, Randolph; Ma, Xubo; Mantovani, Fabio; Mao, Yajun; Mari, Stefano M.; McDonough, William F.; Meng, Guang; Meregaglia, Anselmo; Meroni, Emanuela; Mezzetto, Mauro; Miramonti, Lino; Mueller, Thomas; Naumov, Dmitry; Oberauer, Lothar; Ochoa-Ricoux, Juan Pedro; Olshevskiy, Alexander; Ortica, Fausto; Paoloni, Alessandro; Peng, Haiping; Peng, Jen-Chieh; Previtali, Ezio; Qi, Ming; Qian, Sen; Qian, Xin; Qian, Yongzhong; Qin, Zhonghua; Raffelt, Georg; Ranucci, Gioacchino; Ricci, Barbara; Robens, Markus; Romani, Aldo; Ruan, Xiangdong; Ruan, Xichao; Salamanna, Giuseppe; Shaevitz, Mike; Sinev, Valery; Sirignano, Chiara; Sisti, Monica; Smirnov, Oleg; Soiron, Michael; Stahl, Achim; Stanco, Luca; Steinmann, Jochen; Sun, Xilei; Sun, Yongjie; Taichenachev, Dmitriy; Tang, Jian; Tkachev, Igor; Trzaska, Wladyslaw; van Waasen, Stefan; Volpe, Cristina; Vorobel, Vit; Votano, Lucia; Wang, Chung-Hsiang; Wang, Guoli; Wang, Hao; Wang, Meng; Wang, Ruiguang; Wang, Siguang; Wang, Wei; Wang, Yi; Wang, Yi; Wang, Yifang; Wang, Zhe; Wang, Zheng; Wang, Zhigang; Wang, Zhimin; Wei, Wei; Wen, Liangjian; Wiebusch, Christopher; Wonsak, Björn; Wu, Qun; Wulz, Claudia-Elisabeth; Wurm, Michael; Xi, Yufei; Xia, Dongmei; Xie, Yuguang; Xing, Zhi-zhong; Xu, Jilei; Yan, Baojun; Yang, Changgen; Yang, Chaowen; Yang, Guang; Yang, Lei; Yang, Yifan; Yao, Yu; Yegin, Ugur; Yermia, Frédéric; You, Zhengyun; Yu, Boxiang; Yu, Chunxu; Yu, Zeyuan; Zavatarelli, Sandra; Zhan, Liang; Zhang, Chao; Zhang, Hong-Hao; Zhang, Jiawen; Zhang, Jingbo; Zhang, Qingmin; Zhang, Yu-Mei; Zhang, Zhenyu; Zhao, Zhenghua; Zheng, Yangheng; Zhong, Weili; Zhou, Guorong; Zhou, Jing; Zhou, Li; Zhou, Rong; Zhou, Shun; Zhou, Wenxiong; Zhou, Xiang; Zhou, Yeling; Zhou, Yufeng; Zou, Jiaheng

2016-03-01

The Jiangmen Underground Neutrino Observatory (JUNO), a 20 kton multi-purpose underground liquid scintillator detector, was proposed with the determination of the neutrino mass hierarchy (MH) as a primary physics goal. The excellent energy resolution and the large fiducial volume anticipated for the JUNO detector offer exciting opportunities for addressing many important topics in neutrino and astro-particle physics. In this document, we present the physics motivations and the anticipated performance of the JUNO detector for various proposed measurements. Following an introduction summarizing the current status and open issues in neutrino physics, we discuss how the detection of antineutrinos generated by a cluster of nuclear power plants allows the determination of the neutrino MH at a 3-4σ significance with six years of running of JUNO. The measurement of antineutrino spectrum with excellent energy resolution will also lead to the precise determination of the neutrino oscillation parameters {{sin}}2{θ }12, {{Δ }}{m}212, and | {{Δ }}{m}{ee}2| to an accuracy of better than 1%, which will play a crucial role in the future unitarity test of the MNSP matrix. The JUNO detector is capable of observing not only antineutrinos from the power plants, but also neutrinos/antineutrinos from terrestrial and extra-terrestrial sources, including supernova burst neutrinos, diffuse supernova neutrino background, geoneutrinos, atmospheric neutrinos, and solar neutrinos. As a result of JUNO's large size, excellent energy resolution, and vertex reconstruction capability, interesting new data on these topics can be collected. For example, a neutrino burst from a typical core-collapse supernova at a distance of 10 kpc would lead to ˜5000 inverse-beta-decay events and ˜2000 all-flavor neutrino-proton ES events in JUNO, which are of crucial importance for understanding the mechanism of supernova explosion and for exploring novel phenomena such as collective neutrino oscillations. Detection of neutrinos from all past core-collapse supernova explosions in the visible universe with JUNO would further provide valuable information on the cosmic star-formation rate and the average core-collapse neutrino energy spectrum. Antineutrinos originating from the radioactive decay of uranium and thorium in the Earth can be detected in JUNO with a rate of ˜400 events per year, significantly improving the statistics of existing geoneutrino event samples. Atmospheric neutrino events collected in JUNO can provide independent inputs for determining the MH and the octant of the {θ }23 mixing angle. Detection of the 7Be and 8B solar neutrino events at JUNO would shed new light on the solar metallicity problem and examine the transition region between the vacuum and matter dominated neutrino oscillations. Regarding light sterile neutrino topics, sterile neutrinos with {10}-5 {{{eV}}}2\\lt {{Δ }}{m}412\\lt {10}-2 {{{eV}}}2 and a sufficiently large mixing angle {θ }14 could be identified through a precise measurement of the reactor antineutrino energy spectrum. Meanwhile, JUNO can also provide us excellent opportunities to test the eV-scale sterile neutrino hypothesis, using either the radioactive neutrino sources or a cyclotron-produced neutrino beam. The JUNO detector is also sensitive to several other beyondthe-standard-model physics. Examples include the search for proton decay via the p\\to {K}++\\bar{ν } decay channel, search for neutrinos resulting from dark-matter annihilation in the Sun, search for violation of Lorentz invariance via the sidereal modulation of the reactor neutrino event rate, and search for the effects of non-standard interactions. The proposed construction of the JUNO detector will provide a unique facility to address many outstanding crucial questions in particle and astrophysics in a timely and cost-effective fashion. It holds the great potential for further advancing our quest to understanding the fundamental properties of neutrinos, one of the building blocks of our Universe.

Entorhinal Tau Pathology, Episodic Memory Decline, and Neurodegeneration in Aging.

PubMed

Maass, Anne; Lockhart, Samuel N; Harrison, Theresa M; Bell, Rachel K; Mellinger, Taylor; Swinnerton, Kaitlin; Baker, Suzanne L; Rabinovici, Gil D; Jagust, William J

2018-01-17

The medial temporal lobe (MTL) is an early site of tau accumulation and MTL dysfunction may underlie episodic-memory decline in aging and dementia. Postmortem data indicate that tau pathology in the transentorhinal cortex is common by age 60, whereas spread to neocortical regions and worsening of cognition is associated with β-amyloid (Aβ). We used [ 18 F]AV-1451 and [ 11 C]PiB positron emission tomography, structural MRI, and neuropsychological assessment to investigate how in vivo tau accumulation in temporal lobe regions, Aβ, and MTL atrophy contribute to episodic memory in cognitively normal older adults ( n = 83; age, 77 ± 6 years; 58% female). Stepwise regressions identified tau in MTL regions known to be affected in old age as the best predictor of episodic-memory performance independent of Aβ status. There was no interactive effect of MTL tau with Aβ on memory. Higher MTL tau was related to higher age in the subjects without evidence of Aβ. Among temporal lobe subregions, episodic memory was most strongly related to tau-tracer uptake in the parahippocampal gyrus, particularly the posterior entorhinal cortex, which in our parcellation includes the transentorhinal cortex. In subjects with longitudinal MRI and cognitive data ( n = 57), entorhinal atrophy mirrored patterns of tau pathology and their relationship with memory decline. Our data are consistent with neuropathological studies and further suggest that entorhinal tau pathology underlies memory decline in old age even without Aβ. SIGNIFICANCE STATEMENT Tau tangles and β-amyloid (Aβ) plaques are key lesions in Alzheimer's disease (AD) but both pathologies also occur in cognitively normal older people. Neuropathological data indicate that tau tangles in the medial temporal lobe (MTL) underlie episodic-memory impairments in AD dementia. However, it remains unclear whether MTL tau pathology also accounts for memory impairments often seen in elderly people and how Aβ affects this relationship. Using tau-specific and Aβ-specific positron emission tomography tracers, we show that in vivo MTL tau pathology is associated with episodic-memory performance and MTL atrophy in cognitively normal adults, independent of Aβ. Our data point to MTL tau pathology, particularly in the entorhinal cortex, as a substrate of age-related episodic-memory loss. Copyright © 2018 the authors 0270-6474/18/380530-14$15.00/0.

Modulation of Tau Isoforms Imbalance Precludes Tau Pathology and Cognitive Decline in a Mouse Model of Tauopathy.

PubMed

Espíndola, Sonia Lorena; Damianich, Ana; Alvarez, Rodrigo Javier; Sartor, Manuela; Belforte, Juan Emilio; Ferrario, Juan Esteban; Gallo, Jean-Marc; Avale, María Elena

2018-04-17

The microtubule-associated protein tau regulates myriad neuronal functions, such as microtubule dynamics, axonal transport and neurite outgrowth. Tauopathies are neurodegenerative disorders characterized by the abnormal metabolism of tau, which accumulates as insoluble neuronal deposits. The adult human brain contains equal amounts of tau isoforms with three (3R) or four (4R) repeats of microtubule-binding domains, derived from the alternative splicing of exon 10 (E10) in the tau transcript. Several tauopathies are associated with imbalances of tau isoforms, due to splicing deficits. Here, we used a trans-splicing strategy to shift the inclusion of E10 in a mouse model of tauopathy that produces abnormal excess of 3R tau. Modulating the 3R/4R ratio in the prefrontal cortex led to a significant reduction of pathological tau accumulation concomitant with improvement of neuronal firing and reduction of cognitive impairments. Our results suggest promising potential for the use of RNA reprogramming in human neurodegenerative diseases. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Tau truncation is a productive posttranslational modification of neurofibrillary degeneration in Alzheimer's disease.

PubMed

Kovacech, B; Novak, M

2010-12-01

Deposits of the misfolded neuronal protein tau are major hallmarks of neurodegeneration in Alzheimer's disease (AD) and other tauopathies. The etiology of the transformation process of the intrinsically disordered soluble protein tau into the insoluble misordered aggregate has attracted much attention. Tau undergoes multiple modifications in AD, most notably hyperphosphorylation and truncation. Hyperphosphorylation is widely regarded as the hottest candidate for the inducer of the neurofibrillary pathology. However, the true nature of the impetus that initiates the whole process in the human brains remains unknown. In AD, several site-specific tau cleavages were identified and became connected to the progression of the disease. In addition, western blot analyses of tau species in AD brains reveal multitudes of various truncated forms. In this review we summarize evidence showing that tau truncation alone is sufficient to induce the complete cascade of neurofibrillary pathology, including hyperphosphorylation and accumulation of misfolded insoluble forms of tau. Therefore, proteolytical abnormalities in the stressed neurons and production of aberrant tau cleavage products deserve closer attention and should be considered as early therapeutic targets for Alzheimer's disease.

Predicted sequence of cortical tau and amyloid-β deposition in Alzheimer disease spectrum.

PubMed

Cho, Hanna; Lee, Hye Sun; Choi, Jae Yong; Lee, Jae Hoon; Ryu, Young Hoon; Lee, Myung Sik; Lyoo, Chul Hyoung

2018-04-17

We investigated sequential order between tau and amyloid-β (Aβ) deposition in Alzheimer disease spectrum using a conditional probability method. Two hundred twenty participants underwent 18 F-flortaucipir and 18 F-florbetaben positron emission tomography scans and neuropsychological tests. The presence of tau and Aβ in each region and impairment in each cognitive domain were determined by Z-score cutoffs. By comparing pairs of conditional probabilities, the sequential order of tau and Aβ deposition were determined. Probability for the presence of tau in the entorhinal cortex was higher than that of Aβ in all cortical regions, and in the medial temporal cortices, probability for the presence of tau was higher than that of Aβ. Conversely, in the remaining neocortex above the inferior temporal cortex, probability for the presence of Aβ was always higher than that of tau. Tau pathology in the entorhinal cortex may appear earlier than neocortical Aβ and may spread in the absence of Aβ within the neighboring medial temporal regions. However, Aβ may be required for massive tau deposition in the distant cortical areas. Copyright © 2018 Elsevier Inc. All rights reserved.

Neutrinos

Science.gov Websites

Neutrinos What are they? Neutrinos are members of the Standard Model, belonging to a class of the mass could be and the mass differences between flavors of neutrinos, although there are many current experiments designed to probe this question. The difficulty lies in the fact that neutrinos are

Status and Prospects for Hadron Production Experiments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schroeter, Raphaeel

2010-03-30

The latest results from the HARP, MIPP and NA61 Hadron Production Experiments are reviewed and their implications for neutrinos physics experiments are discussed. We emphasize three neutrino sources: accelerator-based neutrino beams, advanced neutrino sources and atmospheric neutrinos. Finally, prospects from additional forthcoming hadron production measurements are presented.

Probing light sterile neutrino signatures at reactor and Spallation Neutron Source neutrino experiments

NASA Astrophysics Data System (ADS)

Kosmas, T. S.; Papoulias, D. K.; Tórtola, M.; Valle, J. W. F.

2017-09-01

We investigate the impact of a fourth sterile neutrino at reactor and Spallation Neutron Source neutrino detectors. Specifically, we explore the discovery potential of the TEXONO and COHERENT experiments to subleading sterile neutrino effects through the measurement of the coherent elastic neutrino-nucleus scattering event rate. Our dedicated χ2-sensitivity analysis employs realistic nuclear structure calculations adequate for high purity sub-keV threshold Germanium detectors.

Addressing the Majorana vs. Dirac Question Using Neutrino Decays

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kayser, Boris

We explain why it is so hard to determine whether neutrinos are Majorana or Dirac particles as long as the only neutrinos we study are ultra-relativistic. We then show how non-relativistic neutrinos could help, and focus on the angular distributions in the decays of an as-yet-to-be-discovered heavy neutrino $N$. We find that these angular distributions could very well tell us whether neutrinos are Majorana or Dirac particles.

The International Design Study for the Neutrino Factory

DOE Office of Scientific and Technical Information (OSTI.GOV)

Long, K.

2008-02-21

The International Design Study for a future Neutrino Factory and super-beam facility (the ISS) established the physics case for a high-precision programme of long-baseline neutrino-oscillation measurements. The ISS also identified baseline specifications for the Neutrino Factory accelerator complex and the neutrino detector systems. This paper summarises the objectives of the International Design Study for the Neutrino Factory (the IDS-NF). The IDS-NF will build on the work of the ISS to deliver a Reference Design Report for the Neutrino Factory by 2012/13 and an Interim Design Report by 2010/11.

The energy spectrum of atmospheric neutrinos between 2 and 200 TeV with the AMANDA-II detector

NASA Astrophysics Data System (ADS)

Abbasi, R.; Abdou, Y.; Abu-Zayyad, T.; Adams, J.; Aguilar, J. A.; Ahlers, M.; Andeen, K.; Auffenberg, J.; Bai, X.; Baker, M.; Barwick, S. W.; Bay, R.; Bazo Alba, J. L.; Beattie, K.; Beatty, J. J.; Bechet, S.; Becker, J. K.; Becker, K.-H.; Benabderrahmane, M. L.; Berdermann, J.; Berghaus, P.; Berley, D.; Bernardini, E.; Bertrand, D.; Besson, D. Z.; Bissok, M.; Blaufuss, E.; Boersma, D. J.; Bohm, C.; Böser, S.; Botner, O.; Bradley, L.; Braun, J.; Buitink, S.; Carson, M.; Chirkin, D.; Christy, B.; Clem, J.; Clevermann, F.; Cohen, S.; Colnard, C.; Cowen, D. F.; D'Agostino, M. V.; Danninger, M.; De Clercq, C.; Demirörs, L.; Depaepe, O.; Descamps, F.; Desiati, P.; de Vries-Uiterweerd, G.; DeYoung, T.; Díaz-Vélez, J. C.; Dreyer, J.; Dumm, J. P.; Duvoort, M. R.; Ehrlich, R.; Eisch, J.; Ellsworth, R. W.; Engdegård, O.; Euler, S.; Evenson, P. A.; Fadiran, O.; Fazely, A. R.; Fedynitch, A.; Feusels, T.; Filimonov, K.; Finley, C.; Foerster, M. M.; Fox, B. D.; Franckowiak, A.; Franke, R.; Gaisser, T. K.; Gallagher, J.; Ganugapati, R.; Geisler, M.; Gerhardt, L.; Gladstone, L.; Glüsenkamp, T.; Goldschmidt, A.; Goodman, J. A.; Grant, D.; Griesel, T.; Groß, A.; Grullon, S.; Gunasingha, R. M.; Gurtner, M.; Ha, C.; Hallgren, A.; Halzen, F.; Han, K.; Hanson, K.; Helbing, K.; Herquet, P.; Hickford, S.; Hill, G. C.; Hoffman, K. D.; Homeier, A.; Hoshina, K.; Hubert, D.; Huelsnitz, W.; Hülß, J.-P.; Hulth, P. O.; Hultqvist, K.; Hussain, S.; Imlay, R. L.; Ishihara, A.; Jacobsen, J.; Japaridze, G. S.; Johansson, H.; Joseph, J. M.; Kampert, K.-H.; Kappes, A.; Karg, T.; Karle, A.; Kelley, J. L.; Kemming, N.; Kenny, P.; Kiryluk, J.; Kislat, F.; Klein, S. R.; Knops, S.; Köhne, J.-H.; Kohnen, G.; Kolanoski, H.; Köpke, L.; Koskinen, D. J.; Kowalski, M.; Kowarik, T.; Krasberg, M.; Krings, T.; Kroll, G.; Kuehn, K.; Kuwabara, T.; Labare, M.; Lafebre, S.; Laihem, K.; Landsman, H.; Lauer, R.; Lehmann, R.; Lennarz, D.; Lünemann, J.; Madsen, J.; Majumdar, P.; Maruyama, R.; Mase, K.; Matis, H. S.; Matusik, M.; Meagher, K.; Merck, M.; Mészáros, P.; Meures, T.; Middell, E.; Milke, N.; Montaruli, T.; Morse, R.; Movit, S. M.; Münich, K.; Nahnhauer, R.; Nam, J. W.; Naumann, U.; Nießen, P.; Nygren, D. R.; Odrowski, S.; Olivas, A.; Olivo, M.; Ono, M.; Panknin, S.; Paul, L.; Pérez de los Heros, C.; Petrovic, J.; Piegsa, A.; Pieloth, D.; Porrata, R.; Posselt, J.; Price, P. B.; Prikockis, M.; Przybylski, G. T.; Rawlins, K.; Redl, P.; Resconi, E.; Rhode, W.; Ribordy, M.; Rizzo, A.; Rodrigues, J. P.; Roth, P.; Rothmaier, F.; Rott, C.; Roucelle, C.; Ruhe, T.; Rutledge, D.; Ruzybayev, B.; Ryckbosch, D.; Sander, H.-G.; Sarkar, S.; Schatto, K.; Schlenstedt, S.; Schmidt, T.; Schneider, D.; Schukraft, A.; Schultes, A.; Schulz, O.; Schunck, M.; Seckel, D.; Semburg, B.; Seo, S. H.; Sestayo, Y.; Seunarine, S.; Silvestri, A.; Slipak, A.; Spiczak, G. M.; Spiering, C.; Stamatikos, M.; Stanev, T.; Stephens, G.; Stezelberger, T.; Stokstad, R. G.; Stoyanov, S.; Strahler, E. A.; Straszheim, T.; Sullivan, G. W.; Swillens, Q.; Taboada, I.; Tamburro, A.; Tarasova, O.; Tepe, A.; Ter-Antonyan, S.; Tilav, S.; Toale, P. A.; Tosi, D.; Turčan, D.; van Eijndhoven, N.; Vandenbroucke, J.; Van Overloop, A.; van Santen, J.; Voigt, B.; Walck, C.; Waldenmaier, T.; Wallraff, M.; Walter, M.; Wendt, C.; Westerhoff, S.; Whitehorn, N.; Wiebe, K.; Wiebusch, C. H.; Wikström, G.; Williams, D. R.; Wischnewski, R.; Wissing, H.; Woschnagg, K.; Xu, C.; Xu, X. W.; Yodh, G.; Yoshida, S.; Zarzhitsky, P.

2010-08-01

The muon and anti-muon neutrino energy spectrum is determined from 2000-2003 AMANDA telescope data using regularised unfolding. This is the first measurement of atmospheric neutrinos in the energy range 2-200 TeV. The result is compared to different atmospheric neutrino models and it is compatible with the atmospheric neutrinos from pion and kaon decays. No significant contribution from charm hadron decays or extraterrestrial neutrinos is detected. The capabilities to improve the measurement of the neutrino spectrum with the successor experiment IceCube are discussed.

First real-time detection of solar pp neutrinos by Borexino

NASA Astrophysics Data System (ADS)

Pallavicini, M.; Bellini, G.; Benziger, J.; Bick, D.; Bonfini, G.; Bravo, D.; Caccianiga, B.; Calaprice, F.; Caminata, A.; Cavalcante, P.; Chavarria, A.; Chepurnov, A.; D'Angelo, D.; Davini, S.; Derbin, A.; Empl, A.; Etenko, A.; Fomenko, K.; Franco, D.; Gabriele, F.; Galbiati, C.; Gazzana, S.; Ghiano, C.; Giammarchi, M.; Göger-Neff, M.; Goretti, A.; Gromov, M.; Hagner, C.; Hungerford, E.; Ianni, Al.; Ianni, An.; Kayser, M.; Kobychev, V.; Korablëv, D.; Korga, G.; Kryn, D.; Laubenstein, M.; Lehnert, B.; Lewke, T.; Litvinovich, E.; Lombardi, F.; Lombardi, P.; Ludhova, L.; Lukyanchenko, G.; Machulin, I.; Manecki, S.; Maneschg, W.; Marcocci, S.; Meindl, Q.; Meroni, E.; Meyer, M.; Miramonti, L.; Misiaszek, M.; Montuschi, M.; Mosteiro, P.; Muratova, V.; Oberauer, L.; Obolensky, M.; Ortica, F.; Otis, K.; Papp, L.; Perasso, L.; Pocar, A.; Ranucci, G.; Razeto, A.; Re, A.; Romani, A.; Rossi, N.; Saldanha, R.; Salvo, C.; Schönert, S.; Simgen, H.; Skorokhvatov, M.; Smirnov, O.; Sotnikov, A.; Sukhotin, S.; Suvorov, Y.; Tartaglia, R.; Testera, G.; Vignaud, D.; Vogelaar, R. B.; von Feilitzsch, F.; Wang, H.; Winter, J.; Wojcik, M.; Wurm, M.; Zaimidoroga, O.; Zavatarelli, S.; Zuber, K.; Zuzel, G.

2016-07-01

Solar neutrinos have been pivotal to the discovery of neutrino flavour oscillations and are a unique tool to probe the reactions that keep the Sun shine. Although most of solar neutrino components have been directly measured, the neutrinos emitted by the keystone pp reaction, in which two protons fuse to make a deuteron, have so far eluded direct detection. The Borexino experiment, an ultra-pure liquid scintillator detector running at the Laboratori Nazionali del Gran Sasso in Italy, has now filled the gap, providing the first direct real time measurement of pp neutrinos and of the solar neutrino luminosity.

Geometric phase of neutrinos: Differences between Dirac and Majorana neutrinos

NASA Astrophysics Data System (ADS)

Capolupo, A.; Giampaolo, S. M.; Hiesmayr, B. C.; Vitiello, G.

2018-05-01

We analyze the non-cyclic geometric phase for neutrinos. We find that the geometric phase and the total phase associated to the mixing phenomenon provide a theoretical tool to distinguish between Dirac and Majorana neutrinos. Our results hold for neutrinos propagating in vacuum and through the matter. We feed the values of the experimental parameters in our formulas in order to make contact with experiments. Although it remains an open question how the geometric phase of neutrinos could be detected, our theoretical results may open new scenarios in the investigation of the neutrino nature.

The Energy Spectrum of Atmospheric Neutrinos between 2 and 200 TeV with the AMANDA-II Detector

DOE Office of Scientific and Technical Information (OSTI.GOV)

IceCube Collaboration; Abbasi, R.

2010-05-11

The muon and anti-muon neutrino energy spectrum is determined from 2000-2003 AMANDA telescope data using regularised unfolding. This is the first measurement of atmospheric neutrinos in the energy range 2-200 TeV. The result is compared to different atmospheric neutrino models and it is compatible with the atmospheric neutrinos from pion and kaon decays. No significant contribution from charm hadron decays or extraterrestrial neutrinos is detected. The capabilities to improve the measurement of the neutrino spectrum with the successor experiment IceCube are discussed.

Evidence for the MSW effect

NASA Astrophysics Data System (ADS)

Fogli, Gianluigi; Lisi, Eligio

2004-10-01

Recent solar and reactor neutrino data have convincingly established that electron neutrinos and antineutrinos are subject to flavour transitions driven by neutrino masses and mixing. In addition, such data can be used to prove that the interaction of neutrinos in matter modifies the flavour transition pattern with respect to the case of propagation in vacuum, as predicted long ago by Mikheyev, Smirnov and Wolfenstein (MSW). We present a brief review of how the current evidence for MSW solar neutrino transitions has developed in recent years, and how it has been strengthened by the latest reactor neutrino data presented at the Neutrino 2004 Conference.

Supernova Neutrino-Process and Implication in Neutrino Oscillation

NASA Astrophysics Data System (ADS)

Kajino, T.; Aoki, W.; Fujiya, W.; Mathews, G. J.; Yoshida, T.; Shaku, K.; Nakamura, K.; Hayakawa, T.

2012-08-01

We studied the supernova nucleosynthesis induced by neutrino interactions and found that several isotopes of rare elements like 7Li, 11B, 138La, 180Ta and many others are predominantly produced by the neutrino-process in core-collapse supernovae. These isotopes are strongly affected by the neutrino flavor oscillation due to the MSW (Mikheyev-Smirnov-Wolfenstein) effect. We here propose a new novel method to determine the unknown neutrino oscillation parameters, θ13 and mass hierarchy simultaneously from the supernova neutrino-process, combined with the r-process for heavy-element synthsis and the Galactic chemical evolution on light nuclei.

Collective neutrino oscillations and r-process nucleosynthesis in supernovae

NASA Astrophysics Data System (ADS)

Duan, Huaiyu

2012-10-01

Neutrinos can oscillate collectively in a core-collapse supernova. This phenomenon can occur much deeper inside the supernova envelope than what is predicted from the conventional matter-induced Mikheyev-Smirnov-Wolfenstein effect, and hence may have an impact on nucleosynthesis. The oscillation patterns and the r-process yields are sensitive to the details of the emitted neutrino fluxes, the sign of the neutrino mass hierarchy, the modeling of neutrino oscillations and the astrophysical conditions. The effects of collective neutrino oscillations on the r-process will be illustrated using representative late-time neutrino spectra and outflow models.

Decoherence effect in neutrinos produced in microquasar jets

NASA Astrophysics Data System (ADS)

Mosquera, M. E.; Civitarese, O.

2018-04-01

We study the effect of decoherence upon the neutrino spectra produced in microquasar jets. In order to analyse the precession of the polarization vector of neutrinos we have calculated its time evolution by solving the corresponding equations of motion, and by assuming two different scenarios, namely: (i) the mixing between two active neutrinos, and (ii) the mixing between one active and one sterile neutrino. The results of the calculations corresponding to these scenarios show that the onset of decoherence does not depends on the activation of neutrino-neutrino interactions when realistic values of the coupling are used in the calculations. We discuss also the case of neutrinos produced in windy microquasars and compare the results which those obtained with more conventional models of microquasars.

Search for sterile neutrinos in MINOS and MINOS+ using a two-detector fit

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adamson, P.; et al.

2017-10-17

A search for mixing between active neutrinos and light sterile neutrinos has been performed by looking for muon neutrino disappearance in two detectors at baselines of 1.04 km and 735 km, using a combined MINOS and MINOS+ exposure ofmore » $$16.36\\times10^{20}$$ protons-on-target. A simultaneous fit to the charged-current muon neutrino and neutral-current neutrino energy spectra in the two detectors yields no evidence for sterile neutrino mixing using a 3+1 model. The most stringent limit to date is set on the mixing parameter $$\\sin^2\\theta_{24}$$ for most values of the sterile neutrino mass-splitting $$\\Delta m^2_{41} > 10^{-4}$$ eV$^2$.« less

Hiding an elephant: heavy sterile neutrino with large mixing angle does not contradict cosmology

NASA Astrophysics Data System (ADS)

Bezrukov, F.; Chudaykin, A.; Gorbunov, D.

2017-06-01

We study a model of a keV-scale sterile neutrino with a relatively large mixing with the Standard Model sector. Usual considerations predict active generation of such particles in the early Universe, which leads to constraints from the total Dark Matter density and absence of X-ray signal from sterile neutrino decay. These bounds together may deem any attempt of creation of the keV scale sterile neutrino in the laboratory unfeasible. We argue that for models with a hidden sector coupled to the sterile neutrino these bounds can be evaded, opening new perspectives for the direct studies at neutrino experiments such as Troitsk ν-mass and KATRIN. We estimate the generation of sterile neutrinos in scenarios with the hidden sector dynamics keeping the sterile neutrinos either massless or superheavy in the early Universe. In both cases the generation by oscillations from active neutrinos in plasma is suppressed.

Coherent propagation of PeV neutrinos and the dip in the neutrino spectrum at IceCube

NASA Astrophysics Data System (ADS)

Kamada, Ayuki; Yu, Hai-Bo

2015-12-01

The energy spectrum of high-energy neutrinos reported by the IceCube Collaboration shows a dip between 400 TeV and 1 PeV. One intriguing explanation is that high-energy neutrinos scatter with the cosmic neutrino background through an ˜MeV mediator. Taking the density matrix approach, we develop a formalism to study the propagation of PeV neutrinos in the presence of the new neutrino interaction. If the interaction is flavored such as the gauged Lμ-Lτ model we consider, the resonant collision may not suppress the PeV neutrino flux completely. The new force mediator may also contribute to the number of effectively massless degrees of freedom in the early Universe and change the diffusion time of neutrinos from the supernova core. Astrophysical observations such as big bang nucleosynthesis and supernova cooling provide an interesting test for the explanation.

Effect of collisions on neutrino flavor inhomogeneity in a dense neutrino gas

DOE PAGES

Cirigliano, Vincenzo; Paris, Mark W.; Shalgar, Shashank

2017-09-25

We investigate the stability, with respect to spatial inhomogeneity, of a two-dimensional dense neutrino gas. The system exhibits growth of seed inhomogeneity due to nonlinear coherent neutrino self-interactions. In the absence of incoherent collisional effects, we also observe a dependence of this instability growth rate on the neutrino mass spectrum: the normal neutrino mass hierarchy exhibits spatial instability over a larger range of neutrino number density compared to that of the inverted case. Furthermore, we consider the effect of elastic incoherent collisions of the neutrinos with a static background of heavy, nucleon-like scatterers. At small scales, the growth of flavormore » instability can be suppressed by collisions. At large length scales we find, perhaps surprisingly, that for inverted neutrino mass hierarchy incoherent collisions fail to suppress flavor instabilities, independent of the coupling strength.« less

High-energy neutrino follow-up search of gravitational wave event GW150914 with ANTARES and IceCube

NASA Astrophysics Data System (ADS)

Adrián-Martínez, S.; Albert, A.; André, M.; Anghinolfi, M.; Anton, G.; Ardid, M.; Aubert, J.-J.; Avgitas, T.; Baret, B.; Barrios-Martí, J.; Basa, S.; Bertin, V.; Biagi, S.; Bormuth, R.; Bouwhuis, M. C.; Bruijn, R.; Brunner, J.; Busto, J.; Capone, A.; Caramete, L.; Carr, J.; Celli, S.; Chiarusi, T.; Circella, M.; Coleiro, A.; Coniglione, R.; Costantini, H.; Coyle, P.; Creusot, A.; Deschamps, A.; De Bonis, G.; Distefano, C.; Donzaud, C.; Dornic, D.; Drouhin, D.; Eberl, T.; El Bojaddaini, I.; Elsässer, D.; Enzenhöfer, A.; Fehn, K.; Felis, I.; Fusco, L. A.; Galatà, S.; Gay, P.; Geißelsöder, S.; Geyer, K.; Giordano, V.; Gleixner, A.; Glotin, H.; Gracia-Ruiz, R.; Graf, K.; Hallmann, S.; van Haren, H.; Heijboer, A. J.; Hello, Y.; Hernández-Rey, J. J.; Hößl, J.; Hofestädt, J.; Hugon, C.; Illuminati, G.; James, C. W.; de Jong, M.; Jongen, M.; Kadler, M.; Kalekin, O.; Katz, U.; Kießling, D.; Kouchner, A.; Kreter, M.; Kreykenbohm, I.; Kulikovskiy, V.; Lachaud, C.; Lahmann, R.; Lefèvre, D.; Leonora, E.; Loucatos, S.; Marcelin, M.; Margiotta, A.; Marinelli, A.; Martínez-Mora, J. A.; Mathieu, A.; Melis, K.; Michael, T.; Migliozzi, P.; Moussa, A.; Mueller, C.; Nezri, E.; Pǎvǎlaş, G. E.; Pellegrino, C.; Perrina, C.; Piattelli, P.; Popa, V.; Pradier, T.; Racca, C.; Riccobene, G.; Roensch, K.; Saldaña, M.; Samtleben, D. F. E.; Sánchez-Losa, A.; Sanguineti, M.; Sapienza, P.; Schnabel, J.; Schüssler, F.; Seitz, T.; Sieger, C.; Spurio, M.; Stolarczyk, Th.; Taiuti, M.; Trovato, A.; Tselengidou, M.; Turpin, D.; Tönnis, C.; Vallage, B.; Vallée, C.; Van Elewyck, V.; Vivolo, D.; Wagner, S.; Wilms, J.; Zornoza, J. D.; Zúñiga, J.; Aartsen, M. G.; Abraham, K.; Ackermann, M.; Adams, J.; Aguilar, J. A.; Ahlers, M.; Ahrens, M.; Altmann, D.; Anderson, T.; Ansseau, I.; Anton, G.; Archinger, M.; Arguelles, C.; Arlen, T. C.; Auffenberg, J.; Bai, X.; Barwick, S. W.; Baum, V.; Bay, R.; Beatty, J. J.; Becker Tjus, J.; Becker, K.-H.; Beiser, E.; BenZvi, S.; Berghaus, P.; Berley, D.; Bernardini, E.; Bernhard, A.; Besson, D. Z.; Binder, G.; Bindig, D.; Bissok, M.; Blaufuss, E.; Blumenthal, J.; Boersma, D. J.; Bohm, C.; Börner, M.; Bos, F.; Bose, D.; Böser, S.; Botner, O.; Braun, J.; Brayeur, L.; Bretz, H.-P.; Buzinsky, N.; Casey, J.; Casier, M.; Cheung, E.; Chirkin, D.; Christov, A.; Clark, K.; Classen, L.; Coenders, S.; Collin, G. H.; Conrad, J. M.; Cowen, D. F.; Cruz Silva, A. H.; Daughhetee, J.; Davis, J. C.; Day, M.; de André, J. P. A. M.; De Clercq, C.; del Pino Rosendo, E.; Dembinski, H.; De Ridder, S.; Desiati, P.; de Vries, K. D.; de Wasseige, G.; de With, M.; DeYoung, T.; Díaz-Vélez, J. C.; di Lorenzo, V.; Dujmovic, H.; Dumm, J. P.; Dunkman, M.; Eberhardt, B.; Ehrhardt, T.; Eichmann, B.; Euler, S.; Evenson, P. A.; Fahey, S.; Fazely, A. R.; Feintzeig, J.; Felde, J.; Filimonov, K.; Finley, C.; Flis, S.; Fösig, C.-C.; Fuchs, T.; Gaisser, T. K.; Gaior, R.; Gallagher, J.; Gerhardt, L.; Ghorbani, K.; Gier, D.; Gladstone, L.; Glagla, M.; Glüsenkamp, T.; Goldschmidt, A.; Golup, G.; Gonzalez, J. G.; Góra, D.; Grant, D.; Griffith, Z.; Ha, C.; Haack, C.; Haj Ismail, A.; Hallgren, A.; Halzen, F.; Hansen, E.; Hansmann, B.; Hansmann, T.; Hanson, K.; Hebecker, D.; Heereman, D.; Helbing, K.; Hellauer, R.; Hickford, S.; Hignight, J.; Hill, G. C.; Hoffman, K. D.; Hoffmann, R.; Holzapfel, K.; Homeier, A.; Hoshina, K.; Huang, F.; Huber, M.; Huelsnitz, W.; Hulth, P. O.; Hultqvist, K.; In, S.; Ishihara, A.; Jacobi, E.; Japaridze, G. S.; Jeong, M.; Jero, K.; Jones, B. J. P.; Jurkovic, M.; Kappes, A.; Karg, T.; Karle, A.; Katz, U.; Kauer, M.; Keivani, A.; Kelley, J. L.; Kemp, J.; Kheirandish, A.; Kim, M.; Kintscher, T.; Kiryluk, J.; Klein, S. R.; Kohnen, G.; Koirala, R.; Kolanoski, H.; Konietz, R.; Köpke, L.; Kopper, C.; Kopper, S.; Koskinen, D. J.; Kowalski, M.; Krings, K.; Kroll, G.; Kroll, M.; Krückl, G.; Kunnen, J.; Kunwar, S.; Kurahashi, N.; Kuwabara, T.; Labare, M.; Lanfranchi, J. L.; Larson, M. J.; Lennarz, D.; Lesiak-Bzdak, M.; Leuermann, M.; Leuner, J.; Lu, L.; Lünemann, J.; Madsen, J.; Maggi, G.; Mahn, K. B. M.; Mandelartz, M.; Maruyama, R.; Mase, K.; Matis, H. S.; Maunu, R.; McNally, F.; Meagher, K.; Medici, M.; Meier, M.; Meli, A.; Menne, T.; Merino, G.; Meures, T.; Miarecki, S.; Middell, E.; Mohrmann, L.; Montaruli, T.; Morse, R.; Nahnhauer, R.; Naumann, U.; Neer, G.; Niederhausen, H.; Nowicki, S. C.; Nygren, D. R.; Obertacke Pollmann, A.; Olivas, A.; Omairat, A.; O'Murchadha, A.; Palczewski, T.; Pandya, H.; Pankova, D. V.; Paul, L.; Pepper, J. A.; Pérez de los Heros, C.; Pfendner, C.; Pieloth, D.; Pinat, E.; Posselt, J.; Price, P. B.; Przybylski, G. T.; Quinnan, M.; Raab, C.; Rädel, L.; Rameez, M.; Rawlins, K.; Reimann, R.; Relich, M.; Resconi, E.; Rhode, W.; Richman, M.; Richter, S.; Riedel, B.; Robertson, S.; Rongen, M.; Rott, C.; Ruhe, T.; Ryckbosch, D.; Sabbatini, L.; Sander, H.-G.; Sandrock, A.; Sandroos, J.; Sarkar, S.; Schatto, K.; Schimp, M.; Schlunder, P.; Schmidt, T.; Schoenen, S.; Schöneberg, S.; Schönwald, A.; Schumacher, L.; Seckel, D.; Seunarine, S.; Soldin, D.; Song, M.; Spiczak, G. M.; Spiering, C.; Stahlberg, M.; Stamatikos, M.; Stanev, T.; Stasik, A.; Steuer, A.; Stezelberger, T.; Stokstad, R. G.; Stößl, A.; Ström, R.; Strotjohann, N. L.; Sullivan, G. W.; Sutherland, M.; Taavola, H.; Taboada, I.; Tatar, J.; Ter-Antonyan, S.; Terliuk, A.; Tešić, G.; Tilav, S.; Toale, P. A.; Tobin, M. N.; Toscano, S.; Tosi, D.; Tselengidou, M.; Turcati, A.; Unger, E.; Usner, M.; Vallecorsa, S.; Vandenbroucke, J.; van Eijndhoven, N.; Vanheule, S.; van Santen, J.; Veenkamp, J.; Vehring, M.; Voge, M.; Vraeghe, M.; Walck, C.; Wallace, A.; Wallraff, M.; Wandkowsky, N.; Weaver, Ch.; Wendt, C.; Westerhoff, S.; Whelan, B. J.; Wiebe, K.; Wiebusch, C. H.; Wille, L.; Williams, D. R.; Wills, L.; Wissing, H.; Wolf, M.; Wood, T. R.; Woschnagg, K.; Xu, D. L.; Xu, X. W.; Xu, Y.; Yanez, J. P.; Yodh, G.; Yoshida, S.; Zoll, M.; Abbott, B. P.; Abbott, R.; Abbott, T. D.; Abernathy, M. R.; Acernese, F.; Ackley, K.; Adams, C.; Adams, T.; Addesso, P.; Adhikari, R. X.; Adya, V. B.; Affeldt, C.; Agathos, M.; Agatsuma, K.; Aggarwal, N.; Aguiar, O. D.; Aiello, L.; Ain, A.; Ajith, P.; Allen, B.; Allocca, A.; Altin, P. A.; Anderson, S. B.; Anderson, W. G.; Arai, K.; Araya, M. C.; Arceneaux, C. C.; Areeda, J. S.; Arnaud, N.; Arun, K. G.; Ascenzi, S.; Ashton, G.; Ast, M.; Aston, S. M.; Astone, P.; Aufmuth, P.; Aulbert, C.; Babak, S.; Bacon, P.; Bader, M. K. M.; Baker, P. T.; Baldaccini, F.; Ballardin, G.; Ballmer, S. W.; Barayoga, J. C.; Barclay, S. E.; Barish, B. C.; Barker, D.; Barone, F.; Barr, B.; Barsotti, L.; Barsuglia, M.; Barta, D.; Bartlett, J.; Bartos, I.; Bassiri, R.; Basti, A.; Batch, J. C.; Baune, C.; Bavigadda, V.; Bazzan, M.; Behnke, B.; Bejger, M.; Belczynski, C.; Bell, A. S.; Bell, C. J.; Berger, B. K.; Bergman, J.; Bergmann, G.; Berry, C. P. L.; Bersanetti, D.; Bertolini, A.; Betzwieser, J.; Bhagwat, S.; Bhandare, R.; Bilenko, I. A.; Billingsley, G.; Birch, J.; Birney, R.; Biscans, S.; Bisht, A.; Bitossi, M.; Biwer, C.; Bizouard, M. A.; Blackburn, J. K.; Blair, C. D.; Blair, D. G.; Blair, R. M.; Bloemen, S.; Bock, O.; Bodiya, T. P.; Boer, M.; Bogaert, G.; Bogan, C.; Bohe, A.; Bojtos, P.; Bond, C.; Bondu, F.; Bonnand, R.; Boom, B. A.; Bork, R.; Boschi, V.; Bose, S.; Bouffanais, Y.; Bozzi, A.; Bradaschia, C.; Brady, P. R.; Braginsky, V. B.; Branchesi, M.; Brau, J. E.; Briant, T.; Brillet, A.; Brinkmann, M.; Brisson, V.; Brockill, P.; Brooks, A. F.; Brown, D. A.; Brown, D. D.; Brown, N. M.; Buchanan, C. C.; Buikema, A.; Bulik, T.; Bulten, H. J.; Buonanno, A.; Buskulic, D.; Buy, C.; Byer, R. L.; Cadonati, L.; Cagnoli, G.; Cahillane, C.; Calderón Bustillo, J.; Callister, T.; Calloni, E.; Camp, J. B.; Cannon, K. C.; Cao, J.; Capano, C. D.; Capocasa, E.; Carbognani, F.; Caride, S.; Casanueva Diaz, J.; Casentini, C.; Caudill, S.; Cavaglià, M.; Cavalier, F.; Cavalieri, R.; Cella, G.; Cepeda, C. B.; Cerboni Baiardi, L.; Cerretani, G.; Cesarini, E.; Chakraborty, R.; Chalermsongsak, T.; Chamberlin, S. J.; Chan, M.; Chao, S.; Charlton, P.; Chassande-Mottin, E.; Chen, H. Y.; Chen, Y.; Cheng, C.; Chincarini, A.; Chiummo, A.; Cho, H. S.; Cho, M.; Chow, J. H.; Christensen, N.; Chu, Q.; Chua, S.; Chung, S.; Ciani, G.; Clara, F.; Clark, J. A.; Cleva, F.; Coccia, E.; Cohadon, P.-F.; Colla, A.; Collette, C. G.; Cominsky, L.; Constancio, M.; Conte, A.; Conti, L.; Cook, D.; Corbitt, T. R.; Cornish, N.; Corsi, A.; Cortese, S.; Costa, C. A.; Coughlin, M. W.; Coughlin, S. B.; Coulon, J.-P.; Countryman, S. T.; Couvares, P.; Cowan, E. E.; Coward, D. M.; Cowart, M. J.; Coyne, D. C.; Coyne, R.; Craig, K.; Creighton, J. D. E.; Cripe, J.; Crowder, S. G.; Cumming, A.; Cunningham, L.; Cuoco, E.; Dal Canton, T.; Danilishin, S. L.; D'Antonio, S.; Danzmann, K.; Darman, N. S.; Dattilo, V.; Dave, I.; Daveloza, H. P.; Davier, M.; Davies, G. S.; Daw, E. J.; Day, R.; DeBra, D.; Debreczeni, G.; Degallaix, J.; De Laurentis, M.; Deléglise, S.; Del Pozzo, W.; Denker, T.; Dent, T.; Dereli, H.; Dergachev, V.; DeRosa, R. T.; De Rosa, R.; DeSalvo, R.; Dhurandhar, S.; Díaz, M. C.; Di Fiore, L.; Di Giovanni, M.; Di Lieto, A.; Di Pace, S.; Di Palma, I.; Di Virgilio, A.; Dojcinoski, G.; Dolique, V.; Donovan, F.; Dooley, K. L.; Doravari, S.; Douglas, R.; Downes, T. P.; Drago, M.; Drever, R. W. P.; Driggers, J. C.; Du, Z.; Ducrot, M.; Dwyer, S. E.; Edo, T. B.; Edwards, M. C.; Effler, A.; Eggenstein, H.-B.; Ehrens, P.; Eichholz, J.; Eikenberry, S. S.; Engels, W.; Essick, R. C.; Etzel, T.; Evans, M.; Evans, T. M.; Everett, R.; Factourovich, M.; Fafone, V.; Fair, H.; Fairhurst, S.; Fan, X.; Fang, Q.; Farinon, S.; Farr, B.; Farr, W. M.; Favata, M.; Fays, M.; Fehrmann, H.; Fejer, M. M.; Ferrante, I.; Ferreira, E. C.; Ferrini, F.; Fidecaro, F.; Fiori, I.; Fiorucci, D.; Fisher, R. P.; Flaminio, R.; Fletcher, M.; Fournier, J.-D.; Franco, S.; Frasca, S.; Frasconi, F.; Frei, Z.; Freise, A.; Frey, R.; Frey, V.; Fricke, T. T.; Fritschel, P.; Frolov, V. V.; Fulda, P.; Fyffe, M.; Gabbard, H. A. G.; Gair, J. R.; Gammaitoni, L.; Gaonkar, S. G.; Garufi, F.; Gatto, A.; Gaur, G.; Gehrels, N.; Gemme, G.; Gendre, B.; Genin, E.; Gennai, A.; George, J.; Gergely, L.; Germain, V.; Ghosh, Archisman; Ghosh, S.; Giaime, J. A.; Giardina, K. D.; Giazotto, A.; Gill, K.; Glaefke, A.; Goetz, E.; Goetz, R.; Gondan, L.; González, G.; Gonzalez Castro, J. M.; Gopakumar, A.; Gordon, N. A.; Gorodetsky, M. L.; Gossan, S. E.; Gosselin, M.; Gouaty, R.; Graef, C.; Graff, P. B.; Granata, M.; Grant, A.; Gras, S.; Gray, C.; Greco, G.; Green, A. C.; Groot, P.; Grote, H.; Grunewald, S.; Guidi, G. M.; Guo, X.; Gupta, A.; Gupta, M. K.; Gushwa, K. E.; Gustafson, E. K.; Gustafson, R.; Hacker, J. J.; Hall, B. R.; Hall, E. D.; Hammond, G.; Haney, M.; Hanke, M. M.; Hanks, J.; Hanna, C.; Hannam, M. D.; Hanson, J.; Hardwick, T.; Harms, J.; Harry, G. M.; Harry, I. W.; Hart, M. J.; Hartman, M. T.; Haster, C.-J.; Haughian, K.; Heidmann, A.; Heintze, M. C.; Heitmann, H.; Hello, P.; Hemming, G.; Hendry, M.; Heng, I. S.; Hennig, J.; Heptonstall, A. W.; Heurs, M.; Hild, S.; Hoak, D.; Hodge, K. A.; Hofman, D.; Hollitt, S. E.; Holt, K.; Holz, D. E.; Hopkins, P.; Hosken, D. J.; Hough, J.; Houston, E. A.; Howell, E. J.; Hu, Y. M.; Huang, S.; Huerta, E. A.; Huet, D.; Hughey, B.; Husa, S.; Huttner, S. H.; Huynh-Dinh, T.; Idrisy, A.; Indik, N.; Ingram, D. R.; Inta, R.; Isa, H. N.; Isac, J.-M.; Isi, M.; Islas, G.; Isogai, T.; Iyer, B. R.; Izumi, K.; Jacqmin, T.; Jang, H.; Jani, K.; Jaranowski, P.; Jawahar, S.; Jiménez-Forteza, F.; Johnson, W. W.; Jones, D. I.; Jones, R.; Jonker, R. J. G.; Ju, L.; Haris, K.; Kalaghatgi, C. V.; Kalogera, V.; Kandhasamy, S.; Kang, G.; Kanner, J. B.; Karki, S.; Kasprzack, M.; Katsavounidis, E.; Katzman, W.; Kaufer, S.; Kaur, T.; Kawabe, K.; Kawazoe, F.; Kéfélian, F.; Kehl, M. S.; Keitel, D.; Kelley, D. B.; Kells, W.; Kennedy, R.; Key, J. S.; Khalaidovski, A.; Khalili, F. Y.; Khan, I.; Khan, S.; Khan, Z.; Khazanov, E. A.; Kijbunchoo, N.; Kim, C.; Kim, J.; Kim, K.; Kim, Nam-Gyu; Kim, Namjun; Kim, Y.-M.; King, E. J.; King, P. J.; Kinzel, D. L.; Kissel, J. S.; Kleybolte, L.; Klimenko, S.; Koehlenbeck, S. M.; Kokeyama, K.; Koley, S.; Kondrashov, V.; Kontos, A.; Korobko, M.; Korth, W. Z.; Kowalska, I.; Kozak, D. B.; Kringel, V.; Krishnan, B.; Królak, A.; Krueger, C.; Kuehn, G.; Kumar, P.; Kuo, L.; Kutynia, A.; Lackey, B. D.; Landry, M.; Lange, J.; Lantz, B.; Lasky, P. D.; Lazzarini, A.; Lazzaro, C.; Leaci, P.; Leavey, S.; Lebigot, E. O.; Lee, C. H.; Lee, H. K.; Lee, H. M.; Lee, K.; Lenon, A.; Leonardi, M.; Leong, J. R.; Leroy, N.; Letendre, N.; Levin, Y.; Levine, B. M.; Li, T. G. F.; Libson, A.; Littenberg, T. B.; Lockerbie, N. A.; Logue, J.; Lombardi, A. L.; Lord, J. E.; Lorenzini, M.; Loriette, V.; Lormand, M.; Losurdo, G.; Lough, J. D.; Lück, H.; Lundgren, A. P.; Luo, J.; Lynch, R.; Ma, Y.; MacDonald, T.; Machenschalk, B.; MacInnis, M.; Macleod, D. M.; Magaña-Sandoval, F.; Magee, R. M.; Mageswaran, M.; Majorana, E.; Maksimovic, I.; Malvezzi, V.; Man, N.; Mandel, I.; Mandic, V.; Mangano, V.; Mansell, G. L.; Manske, M.; Mantovani, M.; Marchesoni, F.; Marion, F.; Márka, S.; Márka, Z.; Markosyan, A. S.; Maros, E.; Martelli, F.; Martellini, L.; Martin, I. W.; Martin, R. M.; Martynov, D. V.; Marx, J. N.; Mason, K.; Masserot, A.; Massinger, T. J.; Masso-Reid, M.; Matichard, F.; Matone, L.; Mavalvala, N.; Mazumder, N.; Mazzolo, G.; McCarthy, R.; McClelland, D. E.; McCormick, S.; McGuire, S. C.; McIntyre, G.; McIver, J.; McManus, D. J.; McWilliams, S. T.; Meacher, D.; Meadors, G. D.; Meidam, J.; Melatos, A.; Mendell, G.; Mendoza-Gandara, D.; Mercer, R. A.; Merilh, E.; Merzougui, M.; Meshkov, S.; Messenger, C.; Messick, C.; Meyers, P. M.; Mezzani, F.; Miao, H.; Michel, C.; Middleton, H.; Mikhailov, E. E.; Milano, L.; Miller, J.; Millhouse, M.; Minenkov, Y.; Ming, J.; Mirshekari, S.; Mishra, C.; Mitra, S.; Mitrofanov, V. P.; Mitselmakher, G.; Mittleman, R.; Moggi, A.; Mohan, M.; Mohapatra, S. R. P.; Montani, M.; Moore, B. C.; Moore, C. J.; Moraru, D.; Moreno, G.; Morriss, S. R.; Mossavi, K.; Mours, B.; Mow-Lowry, C. M.; Mueller, C. L.; Mueller, G.; Muir, A. W.; Mukherjee, Arunava; Mukherjee, D.; Mukherjee, S.; Mukund, N.; Mullavey, A.; Munch, J.; Murphy, D. J.; Murray, P. G.; Mytidis, A.; Nardecchia, I.; Naticchioni, L.; Nayak, R. K.; Necula, V.; Nedkova, K.; Nelemans, G.; Neri, M.; Neunzert, A.; Newton, G.; Nguyen, T. T.; Nielsen, A. B.; Nissanke, S.; Nitz, A.; Nocera, F.; Nolting, D.; Normandin, M. E. N.; Nuttall, L. K.; Oberling, J.; Ochsner, E.; O'Dell, J.; Oelker, E.; Ogin, G. H.; Oh, J. J.; Oh, S. H.; Ohme, F.; Oliver, M.; Oppermann, P.; Oram, Richard J.; O'Reilly, B.; O'Shaughnessy, R.; Ott, C. D.; Ottaway, D. J.; Ottens, R. S.; Overmier, H.; Owen, B. J.; Pai, A.; Pai, S. A.; Palamos, J. R.; Palashov, O.; Palomba, C.; Pal-Singh, A.; Pan, H.; Pankow, C.; Pannarale, F.; Pant, B. C.; Paoletti, F.; Paoli, A.; Papa, M. A.; Paris, H. R.; Parker, W.; Pascucci, D.; Pasqualetti, A.; Passaquieti, R.; Passuello, D.; Patricelli, B.; Patrick, Z.; Pearlstone, B. L.; Pedraza, M.; Pedurand, R.; Pekowsky, L.; Pele, A.; Penn, S.; Perreca, A.; Phelps, M.; Piccinni, O.; Pichot, M.; Piergiovanni, F.; Pierro, V.; Pillant, G.; Pinard, L.; Pinto, I. M.; Pitkin, M.; Poggiani, R.; Popolizio, P.; Post, A.; Powell, J.; Prasad, J.; Predoi, V.; Premachandra, S. S.; Prestegard, T.; Price, L. R.; Prijatelj, M.; Principe, M.; Privitera, S.; Prix, R.; Prodi, G. A.; Prokhorov, L.; Puncken, O.; Punturo, M.; Puppo, P.; Pürrer, M.; Qi, H.; Qin, J.; Quetschke, V.; Quintero, E. A.; Quitzow-James, R.; Raab, F. J.; Rabeling, D. S.; Radkins, H.; Raffai, P.; Raja, S.; Rakhmanov, M.; Rapagnani, P.; Raymond, V.; Razzano, M.; Re, V.; Read, J.; Reed, C. M.; Regimbau, T.; Rei, L.; Reid, S.; Reitze, D. H.; Rew, H.; Reyes, S. D.; Ricci, F.; Riles, K.; Robertson, N. A.; Robie, R.; Robinet, F.; Rocchi, A.; Rolland, L.; Rollins, J. G.; Roma, V. J.; Romano, J. D.; Romano, R.; Romanov, G.; Romie, J. H.; Rosińska, D.; Rowan, S.; Rüdiger, A.; Ruggi, P.; Ryan, K.; Sachdev, S.; Sadecki, T.; Sadeghian, L.; Salconi, L.; Saleem, M.; Salemi, F.; Samajdar, A.; Sammut, L.; Sanchez, E. J.; Sandberg, V.; Sandeen, B.; Sanders, J. R.; Sassolas, B.; Sathyaprakash, B. S.; Saulson, P. R.; Sauter, O.; Savage, R. L.; Sawadsky, A.; Schale, P.; Schilling, R.; Schmidt, J.; Schmidt, P.; Schnabel, R.; Schofield, R. M. S.; Schönbeck, A.; Schreiber, E.; Schuette, D.; Schutz, B. F.; Scott, J.; Scott, S. M.; Sellers, D.; Sengupta, A. S.; Sentenac, D.; Sequino, V.; Sergeev, A.; Serna, G.; Setyawati, Y.; Sevigny, A.; Shaddock, D. A.; Shah, S.; Shahriar, M. S.; Shaltev, M.; Shao, Z.; Shapiro, B.; Shawhan, P.; Sheperd, A.; Shoemaker, D. H.; Shoemaker, D. M.; Siellez, K.; Siemens, X.; Sigg, D.; Silva, A. D.; Simakov, D.; Singer, A.; Singer, L. P.; Singh, A.; Singh, R.; Singhal, A.; Sintes, A. M.; Slagmolen, B. J. J.; Smith, J. R.; Smith, N. D.; Smith, R. J. E.; Son, E. J.; Sorazu, B.; Sorrentino, F.; Souradeep, T.; Srivastava, A. K.; Staley, A.; Steinke, M.; Steinlechner, J.; Steinlechner, S.; Steinmeyer, D.; Stephens, B. C.; Stone, R.; Strain, K. A.; Straniero, N.; Stratta, G.; Strauss, N. A.; Strigin, S.; Sturani, R.; Stuver, A. L.; Summerscales, T. Z.; Sun, L.; Sutton, P. J.; Swinkels, B. L.; Szczepańczyk, M. J.; Tacca, M.; Talukder, D.; Tanner, D. B.; Tápai, M.; Tarabrin, S. P.; Taracchini, A.; Taylor, R.; Theeg, T.; Thirugnanasambandam, M. P.; Thomas, E. G.; Thomas, M.; Thomas, P.; Thorne, K. A.; Thorne, K. S.; Thrane, E.; Tiwari, S.; Tiwari, V.; Tokmakov, K. V.; Tomlinson, C.; Tonelli, M.; Torres, C. V.; Torrie, C. I.; Töyrä, D.; Travasso, F.; Traylor, G.; Trifirò, D.; Tringali, M. C.; Trozzo, L.; Tse, M.; Turconi, M.; Tuyenbayev, D.; Ugolini, D.; Unnikrishnan, C. S.; Urban, A. L.; Usman, S. A.; Vahlbruch, H.; Vajente, G.; Valdes, G.; van Bakel, N.; van Beuzekom, M.; van den Brand, J. F. J.; Van Den Broeck, C.; Vander-Hyde, D. C.; van der Schaaf, L.; van Heijningen, J. V.; van Veggel, A. A.; Vardaro, M.; Vass, S.; Vasúth, M.; Vaulin, R.; Vecchio, A.; Vedovato, G.; Veitch, J.; Veitch, P. J.; Venkateswara, K.; Verkindt, D.; Vetrano, F.; Viceré, A.; Vinciguerra, S.; Vine, D. J.; Vinet, J.-Y.; Vitale, S.; Vo, T.; Vocca, H.; Vorvick, C.; Voss, D.; Vousden, W. D.; Vyatchanin, S. P.; Wade, A. R.; Wade, L. E.; Wade, M.; Walker, M.; Wallace, L.; Walsh, S.; Wang, G.; Wang, H.; Wang, M.; Wang, X.; Wang, Y.; Ward, R. L.; Warner, J.; Was, M.; Weaver, B.; Wei, L.-W.; Weinert, M.; Weinstein, A. J.; Weiss, R.; Welborn, T.; Wen, L.; Weßels, P.; Westphal, T.; Wette, K.; Whelan, J. T.; Whitcomb, S. E.; White, D. J.; Whiting, B. F.; Williams, R. D.; Williamson, A. R.; Willis, J. L.; Willke, B.; Wimmer, M. H.; Winkler, W.; Wipf, C. C.; Wittel, H.; Woan, G.; Worden, J.; Wright, J. L.; Wu, G.; Yablon, J.; Yam, W.; Yamamoto, H.; Yancey, C. C.; Yap, M. J.; Yu, H.; Yvert, M.; ZadroŻny, A.; Zangrando, L.; Zanolin, M.; Zendri, J.-P.; Zevin, M.; Zhang, F.; Zhang, L.; Zhang, M.; Zhang, Y.; Zhao, C.; Zhou, M.; Zhou, Z.; Zhu, X. J.; Zucker, M. E.; Zuraw, S. E.; Zweizig, J.; Antares Collaboration

2016-06-01

We present the high-energy-neutrino follow-up observations of the first gravitational wave transient GW150914 observed by the Advanced LIGO detectors on September 14, 2015. We search for coincident neutrino candidates within the data recorded by the IceCube and Antares neutrino detectors. A possible joint detection could be used in targeted electromagnetic follow-up observations, given the significantly better angular resolution of neutrino events compared to gravitational waves. We find no neutrino candidates in both temporal and spatial coincidence with the gravitational wave event. Within ±500 s of the gravitational wave event, the number of neutrino candidates detected by IceCube and Antares were three and zero, respectively. This is consistent with the expected atmospheric background, and none of the neutrino candidates were directionally coincident with GW150914. We use this nondetection to constrain neutrino emission from the gravitational-wave event.

Probing Neutrino Hierarchy and Chirality via Wakes.

PubMed

Zhu, Hong-Ming; Pen, Ue-Li; Chen, Xuelei; Inman, Derek

2016-04-08

The relic neutrinos are expected to acquire a bulk relative velocity with respect to the dark matter at low redshifts, and neutrino wakes are expected to develop downstream of the dark matter halos. We propose a method of measuring the neutrino mass based on this mechanism. This neutrino wake will cause a dipole distortion of the galaxy-galaxy lensing pattern. This effect could be detected by combining upcoming lensing surveys with a low redshift galaxy survey or a 21 cm intensity mapping survey, which can map the neutrino flow field. The data obtained with LSST and Euclid should enable us to make a positive detection if the three neutrino masses are quasidegenerate with each neutrino mass of ∼0.1  eV, and a future high precision 21 cm lensing survey would allow the normal hierarchy and inverted hierarchy cases to be distinguished, and even the right-handed Dirac neutrinos may be detectable.

Testing decay of astrophysical neutrinos with incomplete information

NASA Astrophysics Data System (ADS)

Bustamante, Mauricio; Beacom, John F.; Murase, Kohta

2017-03-01

Neutrinos mix and have mass differences, so decays from one to another must occur. But how fast? The best direct limits on nonradiative decays, based on solar and atmospheric neutrinos, are weak, τ ≳10-3 s (m /eV ) or much worse. Greatly improved sensitivity, τ ˜1 03 s (m /eV ), will eventually be obtained using neutrinos from distant astrophysical sources, but large uncertainties—in neutrino properties, source properties, and detection aspects—do not allow this yet. However, there is a way forward now. We show that IceCube diffuse neutrino measurements, supplemented by improvements expected in the near term, can increase sensitivity to τ ˜10 s (m /eV ) for all neutrino mass eigenstates. We provide a road map for the necessary analyses and show how to manage the many uncertainties. If limits are set, this would definitively rule out the long-considered possibility that neutrino decay affects solar, atmospheric, or terrestrial neutrino experiments.

A search for muon neutrino to electron neutrino oscillation mediated by sterile neutrinos in MINOS+

NASA Astrophysics Data System (ADS)

Germani, Stefano; Schreckenberger, Adam P.

2017-09-01

The MINOS experiment made precision measurements of the neutrino oscillation parameters that are governed by the atmospheric mass-squared splitting. These measurements were made with data that were collected while the NuMI muon neutrino beam operated in a low energy mode that peaks around 3 GeV. Today the NuMI beam is running with a higher energy mode that produces a neutrino energy spectrum that peaks around 7 GeV, allowing the MINOS+ experiment to probe neutrino oscillation phenomena that could potentially be governed by a fourth mass-squared splitting. If observed, the presence of a fourth mass-squared splitting would be compelling evidence for a sterile neutrino state. In this analysis, we will present the results of a search for νµ → νe oscillation mediated by sterile neutrinos in MINOS+. The results will be contrasted against the measurements made by the LSND experiment.

Symmetry breaking, and the effect of matter density on neutrino oscillation

NASA Astrophysics Data System (ADS)

Mohseni Sadjadi, H.; Khosravi Karchi, A. P.

2018-04-01

A proposal for the neutrino mass, based on neutrino-scalar field interaction, is introduced. The scalar field is also non-minimally coupled to the Ricci scalar, and hence relates the neutrino mass to the matter density. In a dense region, the scalar field obeys the Z2 symmetry, and the neutrino is massless. In a dilute region, the Z2 symmetry breaks and neutrino acquires mass from the non-vanishing expectation value of the scalar field. We consider this scenario in the framework of a spherical dense object whose outside is a dilute region. In this background, we study the neutrino flavors oscillation, along with the consequences of the theory on oscillation length and MSW effect. This preliminary model may shed some lights on the existing anomalies within the neutrino data, concerning the different oscillating behavior of the neutrinos in regions with different densities.

Nuclear physics for geo-neutrino studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fiorentini, Gianni; Istituto Nazionale di Fisica Nucleare, Sezione di Ferrara, I-44100 Ferrara; Ianni, Aldo

2010-03-15

Geo-neutrino studies are based on theoretical estimates of geo-neutrino spectra. We propose a method for a direct measurement of the energy distribution of antineutrinos from decays of long-lived radioactive isotopes. We present preliminary results for the geo-neutrinos from {sup 214}Bi decay, a process that accounts for about one-half of the total geo-neutrino signal. The feeding probability of the lowest state of {sup 214}Bi--the most important for geo-neutrino signal--is found to be p{sub 0}=0.177+-0.004 (stat){sub -0.001}{sup +0.003} (sys), under the hypothesis of universal neutrino spectrum shape (UNSS). This value is consistent with the (indirect) estimate of the table of isotopes. Wemore » show that achievable larger statistics and reduction of systematics should allow for the testing of possible distortions of the neutrino spectrum from that predicted using the UNSS hypothesis. Implications on the geo-neutrino signal are discussed.« less

Accelerator-based Neutrino Physics at Fermilab

NASA Astrophysics Data System (ADS)

Dukes, Edmond

2008-10-01

The discovery of neutrino mass has excited great interest in elucidating the properties of neutrinos and their role in nature. Experiments around the world take advantage of solar, atmospheric, reactor, and accelerator sources of neutrinos. Accelerator-based sources are particularly convenient since their parameters can be tuned to optimize the measurement in question. At Fermilab an extensive neutrino program includes the MiniBooNE, SciBooNE, and MINOS experiments. Two major new experiments, MINERvA and NOvA, are being constructed, plans for a high-intensity neutrino source to DUSEL are underway, and an R&D effort towards a large liquid argon detector is being pursued. The NOvA experiment intends to search for electron neutrino appearance using a massive surface detector 811 km from Fermilab. In addition to measuring the last unknown mixing angle, theta(13), NOvA has the possibility of seeing matter-antimatter asymmetries in neutrinos and resolving the ordering of the neutrino mass states.

Neutrinos in large extra dimensions and short-baseline νe appearance

NASA Astrophysics Data System (ADS)

Carena, Marcela; Li, Ying-Ying; Machado, Camila S.; Machado, Pedro A. N.; Wagner, Carlos E. M.

2017-11-01

We show that, in the presence of bulk masses, sterile neutrinos propagating in large extra dimensions (LED) can induce electron-neutrino appearance effects. This is in contrast to what happens in the standard LED scenario, and hence LED models with explicit bulk masses have the potential to address the MiniBooNE and LSND appearance results as well as the reactor and Gallium anomalies. A special feature in our scenario is that the mixing of the first Kaluza-Klein modes to active neutrinos can be suppressed, making the contribution of heavier sterile neutrinos to oscillations relatively more important. We study the implications of this neutrino mass generation mechanism for current and future neutrino oscillation experiments and show that the Short Baseline Neutrino Program at Fermilab will be able to efficiently probe such a scenario. In addition, this framework leads to massive Dirac neutrinos and thus precludes any signal in neutrinoless double beta decay experiments.

Constraining astrophysical neutrino flavor composition from leptonic unitarity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, Xun-Jie; He, Hong-Jian; Rodejohann, Werner, E-mail: xunjie.xu@gmail.com, E-mail: hjhe@tsinghua.edu.cn, E-mail: werner.rodejohann@mpi-hd.mpg.de

2014-12-01

The recent IceCube observation of ultra-high-energy astrophysical neutrinos has begun the era of neutrino astronomy. In this work, using the unitarity of leptonic mixing matrix, we derive nontrivial unitarity constraints on the flavor composition of astrophysical neutrinos detected by IceCube. Applying leptonic unitarity triangles, we deduce these unitarity bounds from geometrical conditions, such as triangular inequalities. These new bounds generally hold for three flavor neutrinos, and are independent of any experimental input or the pattern of lepton mixing. We apply our unitarity bounds to derive general constraints on the flavor compositions for three types of astrophysical neutrino sources (and theirmore » general mixture), and compare them with the IceCube measurements. Furthermore, we prove that for any sources without ν{sub τ} neutrinos, a detected ν{sub μ} flux ratio < 1/4 will require the initial flavor composition with more ν{sub e} neutrinos than ν{sub μ} neutrinos.« less

Simulating nonlinear neutrino flavor evolution

NASA Astrophysics Data System (ADS)

Duan, H.; Fuller, G. M.; Carlson, J.

2008-10-01

We discuss a new kind of astrophysical transport problem: the coherent evolution of neutrino flavor in core collapse supernovae. Solution of this problem requires a numerical approach which can simulate accurately the quantum mechanical coupling of intersecting neutrino trajectories and the associated nonlinearity which characterizes neutrino flavor conversion. We describe here the two codes developed to attack this problem. We also describe the surprising phenomena revealed by these numerical calculations. Chief among these is that the nonlinearities in the problem can engineer neutrino flavor transformation which is dramatically different to that in standard Mikheyev Smirnov Wolfenstein treatments. This happens even though the neutrino mass-squared differences are measured to be small, and even when neutrino self-coupling is sub-dominant. Our numerical work has revealed potential signatures which, if detected in the neutrino burst from a Galactic core collapse event, could reveal heretofore unmeasurable properties of the neutrinos, such as the mass hierarchy and vacuum mixing angle θ13.

Neutrino Astronomy with IceCube

NASA Astrophysics Data System (ADS)

Meagher, Kevin J.

The IceCube Neutrino Observatory is a cubic kilometer neutrino telescope located at the Geographic South Pole. Cherenkov radiation emitted by charged secondary particles from neutrino interactions is observed by IceCube using an array of 5160 photomultiplier tubes embedded between a depth of 1.5 km to 2.5 km in the Antarctic glacial ice. The detection of astrophysical neutrinos is a primary goal of IceCube and has now been realized with the discovery of a diffuse, high-energy flux consisting of neutrino events from tens of TeV up to several PeV. Many analyses have been performed to identify the source of these neutrinos: correlations with active galactic nuclei, gamma-ray bursts, and the galactic plane. IceCube also conducts multi-messenger campaigns to alert other observatories of possible neutrino transients in real-time. However, the source of these neutrinos remains elusive as no corresponding electromagnetic counterparts have been identified. This proceeding will give an overview of the detection principles of IceCube, the properties of the observed astrophysical neutrinos, the search for corresponding sources (including real-time searches), and plans for a next-generation neutrino detector, IceCube-Gen2.

Simulation of coherent nonlinear neutrino flavor transformation in the supernova environment: Correlated neutrino trajectories

NASA Astrophysics Data System (ADS)

Duan, Huaiyu; Fuller, George M.; Carlson, J.; Qian, Yong-Zhong

2006-11-01

We present results of large-scale numerical simulations of the evolution of neutrino and antineutrino flavors in the region above the late-time post-supernova-explosion proto-neutron star. Our calculations are the first to allow explicit flavor evolution histories on different neutrino trajectories and to self-consistently couple flavor development on these trajectories through forward scattering-induced quantum coupling. Employing the atmospheric-scale neutrino mass-squared difference (|δm2|≃3×10-3eV2) and values of θ13 allowed by current bounds, we find transformation of neutrino and antineutrino flavors over broad ranges of energy and luminosity in roughly the “bi-polar” collective mode. We find that this large-scale flavor conversion, largely driven by the flavor off-diagonal neutrino-neutrino forward scattering potential, sets in much closer to the proto-neutron star than simple estimates based on flavor-diagonal potentials and Mikheyev-Smirnov-Wolfenstein evolution would indicate. In turn, this suggests that models of r-process nucleosynthesis sited in the neutrino-driven wind could be affected substantially by active-active neutrino flavor mixing, even with the small measured neutrino mass-squared differences.

Another look at the impact of an eV-mass sterile neutrino on the effective neutrino mass of neutrinoless double-beta decays

NASA Astrophysics Data System (ADS)

Liu, Jun-Hao; Zhou, Shun

2018-01-01

The possible existence of an eV-mass sterile neutrino, slightly mixing with ordinary active neutrinos, is not yet excluded by neutrino oscillation experiments. Assuming neutrinos to be Majorana particles, we explore the impact of such a sterile neutrino on the effective neutrino mass of neutrinoless double-beta decays 〈m〉ee‧≡ m 1|V e1|2eiρ + m 2|V e2|2 + m 3|V e3|2eiσ + m 4|V e4|2eiω, where mi and Vei (for i = 1, 2, 3, 4) denote respectively the absolute masses and the first-row elements of the 4 × 4 neutrino flavor mixing matrix V, for which a full parametrization involves three Majorana-type CP-violating phases {ρ,σ,ω}. A zero effective neutrino mass |〈m〉ee‧| = 0 is possible, no matter whether three active neutrinos take the normal or inverted mass ordering, and its implications for the parameter space are examined in great detail. In particular, given the best-fit values of m4 ≈ 1.3eV and |Ve4|2 ≈ 0.019 from the latest global analysis of neutrino oscillation data, a three-dimensional view of |〈m〉ee‧| in the (mlightest,ρ)-plane is presented and further compared with that of the counterpart |〈m〉ee| in the absence of any sterile neutrino.