2,815 research outputs found
Overexpression of wild-type human APP in mice causes cognitive déficits and pathological features unrelated to Abeta levels
Transgenic mice expressing mutant human amyloid precursor protein (APP) develop an age-dependent
amyloid pathology and memory deficits, but no overt neuronal loss. Here, in mice overexpressing wild-type
human APP (hAPPwt) we found an early memory impairment, particularly in the water maze and to a lesser
extent in the object recognition task, but β-amyloid peptide (Aβ42) was barely detectable in the
hippocampus. In these mice, hAPP processing was basically non-amyloidogenic, with high levels of APP
carboxy-terminal fragments, C83 and APP intracellular domain. A tau pathology with an early increase in the
levels of phosphorylated tau in the hippocampus, a likely consequence of enhanced ERK1/2 activation, was
also observed. Furthermore, these mice presented a loss of synapse-associated proteins: PSD95, AMPA and
NMDA receptor subunits and phosphorylated CaMKII. Importantly, signs of neurodegeneration were found in
the hippocampal CA1 subfield and in the entorhinal cortex that were associated to a marked loss of MAP2
immunoreactivity. Conversely, in mice expressing mutant hAPP, high levels of Aβ42 were found in the
hippocampus, but no signs of neurodegeneration were apparent. The results support the notion of Aβ-
independent pathogenic pathways in Alzheimer's disease
Early Changes in Hippocampal Eph Receptors Precede the Onset of Memory Decline in Mouse Models of Alzheimer’s Disease
Abstract. Synapse loss occurs early in Alzheimer’s disease (AD) and is considered the best pathological correlate of cognitive
decline. Ephrins and Eph receptors are involved in regulation of excitatory neurotransmission and play a role in cytoskeleton
remodeling. We asked whether alterations in Eph receptors could underlie cognitive impairment in an AD mouse model
overexpressing human amyloid-β protein precursor (hAβPP) with familial mutations (hAβPPswe-ind mice). We found that
EphA4 and EphB2 receptors were reduced in the hippocampus before the development of impaired object recognition and spatial
memory. Similar results were obtained in another line of transgenic AβPP mice, Tg2576. A reduction in Eph receptor levels
was also found in postmortem hippocampal tissue from patients with incipient AD. At the time of onset of memory decline
in hAβPPswe-ind mice, no change in surface expression of AMPA or NMDA receptor subunits was apparent, but we found
changes in Eph-receptor downstream signaling, in particular a decrease in membrane-associated phospho-cofilin levels that may
cause cytoskeletal changes and disrupted synaptic activity. Consistent with this finding, Eph receptor activation in cell culture
increased phospho-cofilin levels. The results suggest that alterations in Eph receptors may play a role in synaptic dysfunction in
the hippocampus leading to cognitive impairment in a model of AD
The status of the Quijote multi-frequency instrument
The QUIJOTE-CMB project has been described in previous publications. Here we present the current status of the QUIJOTE multi-frequency instrument (MFI) with five separate polarimeters (providing 5 independent sky pixels): two which operate at 10-14 GHz, two which operate at 16-20 GHz, and a central polarimeter at 30 GHz. The optical arrangement includes 5 conical corrugated feedhorns staring into a dual reflector crossed-draconian system, which provides optimal cross-polarization properties (designed to be < -35 dB) and symmetric beams. Each horn feeds a novel cryogenic on-axis rotating polar modulator which can rotate at a speed of up to 1 Hz. The science driver for this first instrument is the characterization of the galactic emission. The polarimeters use the polar modulator to derive linear polar parameters Q, U and I and switch out various systematics. The detection system provides optimum sensitivity through 2 correlated and 2 total power channels. The system is calibrated using bright polarized celestial sources and through a secondary calibration source and antenna. The acquisition system, telescope control and housekeeping are all linked through a real-time gigabit Ethernet network. All communication, power and helium gas are passed through a central rotary joint. The time stamp is synchronized to a GPS time signal. The acquisition software is based on PLCs written in Beckhoffs TwinCat and ethercat. The user interface is written in LABVIEW. The status of the QUIJOTE MFI will be presented including pre-commissioning results and laboratory testing
Therapeutic Effect of a Novel Oxazolidinone, DA-7867, in BALB/c Mice Infected with Nocardia brasiliensis
Actinomycetoma is an infectious disease of tropical and subtropical regions produced by actinobacteria of the genera Nocardia, Streptomyces, and Actinomadura. Therapeutic alternatives are scarce and include trimethoprim-sulfamethoxazole, diaminodiphenylsulfone, amoxicillin-clavulanate, imipenem, and amikacin. Oxazolidinones are a new class of antimicrobials with a completely different cellular target; the first compound in the market, linezolid, was introduced in the year 2000. It is active against many species of Nocardia and other aerobic actinomycetes; however, the long-term application in human subjects produces side effects including peripheral neuropathy and mielossupression. Therefore, it is important to screen other oxazolidinones with higher activity and less toxicity. In the present work, we tested DA-7867, a new oxazolidinone, in an experimental mouse model. The drug is active in vivo and decreases the production of lesions using only one dose a day in contrast to linezolid, which needs to be injected three times a day. Although it was tested on N. brasiliensis, it can possibly be active (once it is accepted for its use in humans) against Actinomadura spp and Streptomyces spp, which are frequently found in places of Africa and India where actinomycetoma is also an important consult in dermatology
Measurement of the lifetime
Using a data set corresponding to an integrated luminosity of ,
collected by the LHCb experiment in collisions at centre-of-mass energies
of 7 and 8 TeV, the effective lifetime in the
decay mode, , is measured to be ps. Assuming
conservation, corresponds to the lifetime of the light
mass eigenstate. This is the first measurement of the effective
lifetime in this decay mode.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-017.htm
Study of and decays and determination of the CKM angle
We report a study of the suppressed and favored
decays, where the neutral meson is detected
through its decays to the and CP-even and
final states. The measurement is carried out using a proton-proton
collision data sample collected by the LHCb experiment, corresponding to an
integrated luminosity of 3.0~fb. We observe the first significant
signals in the CP-even final states of the meson for both the suppressed
and favored modes, as well as
in the doubly Cabibbo-suppressed final state of the decay. Evidence for the ADS suppressed decay , with , is also presented. From the observed
yields in the , and their
charge conjugate decay modes, we measure the value of the weak phase to be
. This is one of the most precise
single-measurement determinations of to date.Comment: 22 pages, 9 figures; All figures and tables, along with any
supplementary material and additional information, are available at
https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-020.htm
Observation of an Excited Bc+ State
Using pp collision data corresponding to an integrated luminosity of 8.5 fb-1 recorded by the LHCb experiment at center-of-mass energies of s=7, 8, and 13 TeV, the observation of an excited Bc+ state in the Bc+π+π- invariant-mass spectrum is reported. The observed peak has a mass of 6841.2±0.6(stat)±0.1(syst)±0.8(Bc+) MeV/c2, where the last uncertainty is due to the limited knowledge of the Bc+ mass. It is consistent with expectations of the Bc∗(2S31)+ state reconstructed without the low-energy photon from the Bc∗(1S31)+→Bc+γ decay following Bc∗(2S31)+→Bc∗(1S31)+π+π-. A second state is seen with a global (local) statistical significance of 2.2σ (3.2σ) and a mass of 6872.1±1.3(stat)±0.1(syst)±0.8(Bc+) MeV/c2, and is consistent with the Bc(2S10)+ state. These mass measurements are the most precise to date
Amplitude analysis of decays
The Dalitz plot distribution of decays
is studied using a data sample corresponding to of
collision data recorded by the LHCb experiment during 2011 and 2012. The data
are described by an amplitude model that contains contributions from
intermediate , , and
resonances. The model also contains components to describe broad structures,
including the and resonances, in the
S-wave and the S- and P-waves. The masses and widths of the
and resonances are measured, as are the complex
amplitudes and fit fractions for all components included in the amplitude
model. The model obtained will be an integral part of a future determination of
the angle of the CKM quark mixing matrix using decays.Comment: 33 pages, 12 figures; updated for publicatio
Measurement of the mass and lifetime of the baryon
A proton-proton collision data sample, corresponding to an integrated
luminosity of 3 fb collected by LHCb at and 8 TeV, is used
to reconstruct , decays. Using the , decay mode for calibration, the lifetime ratio and absolute
lifetime of the baryon are measured to be \begin{align*}
\frac{\tau_{\Omega_b^-}}{\tau_{\Xi_b^-}} &= 1.11\pm0.16\pm0.03, \\
\tau_{\Omega_b^-} &= 1.78\pm0.26\pm0.05\pm0.06~{\rm ps}, \end{align*} where the
uncertainties are statistical, systematic and from the calibration mode (for
only). A measurement is also made of the mass difference,
, and the corresponding mass, which
yields \begin{align*} m_{\Omega_b^-}-m_{\Xi_b^-} &= 247.4\pm3.2\pm0.5~{\rm
MeV}/c^2, \\ m_{\Omega_b^-} &= 6045.1\pm3.2\pm 0.5\pm0.6~{\rm MeV}/c^2.
\end{align*} These results are consistent with previous measurements.Comment: 11 pages, 5 figures, All figures and tables, along with any
supplementary material and additional information, are available at
https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-008.htm
Study of boson production in association with beauty and charm
The associated production of a boson with a jet originating from either a
light parton or heavy-flavor quark is studied in the forward region using
proton-proton collisions. The analysis uses data corresponding to integrated
luminosities of 1.0 and collected with the LHCb detector
at center-of-mass energies of 7 and 8 TeV, respectively. The bosons are
reconstructed using the decay and muons with a transverse
momentum, , larger than 20 GeV in the pseudorapidity range
GeV
and . The sum of the muon and jet momenta must satisfy
GeV. The fraction of jet events that originate from beauty
and charm quarks is measured, along with the charge asymmetries of the
and production cross-sections. The ratio of the jet to
jet production cross-sections is also measured using the
decay. All results are in agreement with Standard Model predictions
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