157 research outputs found
Improved Learning and Memory in Aged Mice Deficient in Amyloid β-Degrading Neutral Endopeptidase
BACKGROUND: Neutral endopeptidase, also known as neprilysin and abbreviated NEP, is considered to be one of the key enzymes in initial human amyloid-beta (Abeta) degradation. The aim of our study was to explore the impact of NEP deficiency on the initial development of dementia-like symptoms in mice. METHODOLOGY/PRINCIPAL FINDINGS: We found that while endogenous Abeta concentrations were elevated in the brains of NEP-knockout mice at all investigated age groups, immunohistochemical analysis using monoclonal antibodies did not detect any Abeta deposits even in old NEP knockout mice. Surprisingly, tests of learning and memory revealed that the ability to learn was not reduced in old NEP-deficient mice but instead had significantly improved, and sustained learning and memory in the aged mice was congruent with improved long-term potentiation (LTP) in brain slices of the hippocampus and lateral amygdala. Our data suggests a beneficial effect of pharmacological inhibition of cerebral NEP on learning and memory in mice due to the accumulation of peptides other than Abeta degradable by NEP. By conducting degradation studies and peptide measurements in the brain of both genotypes, we identified two neuropeptide candidates, glucagon-like peptide 1 and galanin, as first potential candidates to be involved in the improved learning in aged NEP-deficient mice. CONCLUSIONS/SIGNIFICANCE: Thus, the existence of peptides targeted by NEP that improve learning and memory in older individuals may represent a promising avenue for the treatment of neurodegenerative diseases
Measurement of B(t->Wb)/B(t->Wq) at the Collider Detector at Fermilab
We present a measurement of the ratio of top-quark branching fractions R= B(t
-> Wb)/B(t -> Wq), where q can be a b, s or a d quark, using lepton-plus-jets
and dilepton data sets with integrated luminosity of ~162 pb^{-1} collected
with the Collider Detector at Fermilab during Run II of the Tevatron. The
measurement is derived from the relative numbers of t-tbar events with
different multiplicity of identified secondary vertices. We set a lower limit
of R > 0.61 at 95% confidence level.Comment: 7 pages, 2 figures, published in Physical Review Letters; changes
made to be consistent with published versio
Search for ZZ and ZW Production in ppbar Collisions at sqrt(s) = 1.96 TeV
We present a search for ZZ and ZW vector boson pair production in ppbar
collisions at sqrt(s) = 1.96 TeV using the leptonic decay channels ZZ --> ll nu
nu, ZZ --> l l l' l' and ZW --> l l l' nu. In a data sample corresponding to an
integrated luminosity of 194 pb-1 collected with the Collider Detector at
Fermilab, 3 candidate events are found with an expected background of 1.0 +/-
0.2 events. We set a 95% confidence level upper limit of 15.2 pb on the cross
section for ZZ plus ZW production, compared to the standard model prediction of
5.0 +/- 0.4 pb.Comment: 7 pages, 2 figures. This version is accepted for publication by Phys.
Rev. D Rapid Communication
Measurement of the Cross Section for Prompt Diphoton Production in p-pbar Collisions at sqrt(s) = 1.96 TeV
We report a measurement of the rate of prompt diphoton production in
collisions at using a data sample of 207
pb collected with the upgraded Collider Detector at Fermilab (CDF II).
The background from non-prompt sources is determined using a statistical method
based on differences in the electromagnetic showers. The cross section is
measured as a function of the diphoton mass, the transverse momentum of the
diphoton system, and the azimuthal angle between the two photons and is found
to be consistent with perturbative QCD predictions.Comment: 7 pages, 3 figures,revtex4. Version accepted by PRL, but with cross
section tables i
Gastrin-releasing peptide receptor-based targeting using bombesin analogues is superior to metabolism-based targeting using choline for in vivo imaging of human prostate cancer xenografts
Purpose: Prostate cancer (PC) is a major health problem. Overexpression of the gastrin-releasing peptide receptor (GRPR) in PC, but not in the hyperplastic prostate, provides a promising target for staging and monitoring of PC. Based on the assumption that cancer cells have increased metabolic activity, metabolism-based tracers are also being used for PC imaging. We compared GRPR-based targeting using the68Ga-labelled bombesin analogue AMBA with metabolism-based tar
Comparative genetic architectures of schizophrenia in East Asian and European populations
Schizophrenia is a debilitating psychiatric disorder with approximately 1% lifetime risk globally. Large-scale schizophrenia genetic studies have reported primarily on European ancestry samples, potentially missing important biological insights. Here, we report the largest study to date of East Asian participants (22,778 schizophrenia cases and 35,362 controls), identifying 21 genome-wide-significant associations in 19 genetic loci. Common genetic variants that confer risk for schizophrenia have highly similar effects between East Asian and European ancestries (genetic correlation = 0.98 ± 0.03), indicating that the genetic basis of schizophrenia and its biology are broadly shared across populations. A fixed-effect meta-analysis including individuals from East Asian and European ancestries identified 208 significant associations in 176 genetic loci (53 novel). Trans-ancestry fine-mapping reduced the sets of candidate causal variants in 44 loci. Polygenic risk scores had reduced performance when transferred across ancestries, highlighting the importance of including sufficient samples of major ancestral groups to ensure their generalizability across populations
Observations of Ly Emitters at High Redshift
In this series of lectures, I review our observational understanding of
high- Ly emitters (LAEs) and relevant scientific topics. Since the
discovery of LAEs in the late 1990s, more than ten (one) thousand(s) of LAEs
have been identified photometrically (spectroscopically) at to . These large samples of LAEs are useful to address two major astrophysical
issues, galaxy formation and cosmic reionization. Statistical studies have
revealed the general picture of LAEs' physical properties: young stellar
populations, remarkable luminosity function evolutions, compact morphologies,
highly ionized inter-stellar media (ISM) with low metal/dust contents, low
masses of dark-matter halos. Typical LAEs represent low-mass high- galaxies,
high- analogs of dwarf galaxies, some of which are thought to be candidates
of population III galaxies. These observational studies have also pinpointed
rare bright Ly sources extended over kpc, dubbed
Ly blobs, whose physical origins are under debate. LAEs are used as
probes of cosmic reionization history through the Ly damping wing
absorption given by the neutral hydrogen of the inter-galactic medium (IGM),
which complement the cosmic microwave background radiation and 21cm
observations. The low-mass and highly-ionized population of LAEs can be major
sources of cosmic reionization. The budget of ionizing photons for cosmic
reionization has been constrained, although there remain large observational
uncertainties in the parameters. Beyond galaxy formation and cosmic
reionization, several new usages of LAEs for science frontiers have been
suggested such as the distribution of {\sc Hi} gas in the circum-galactic
medium and filaments of large-scale structures. On-going programs and future
telescope projects, such as JWST, ELTs, and SKA, will push the horizons of the
science frontiers.Comment: Lecture notes for `Lyman-alpha as an Astrophysical and Cosmological
Tool', Saas-Fee Advanced Course 46. Verhamme, A., North, P., Cantalupo, S., &
Atek, H. (eds.) --- 147 pages, 103 figures. Abstract abridged. Link to the
lecture program including the video recording and ppt files :
https://obswww.unige.ch/Courses/saas-fee-2016/program.cg
Search for electroweak single top quark production in ppbar collisions at sqrt{s}=1.96 TeV
We report on a search for Standard Model t-channel and s-channel single top
quark production in ppbar collisions at a center of mass energy of 1.96 TeV. We
use a data sample corresponding to 162 pb^{-1} recorded by the upgraded
Collider Detector at Fermilab. We find no significant evidence for electroweak
top quark production and set upper limits at the 95% confidence level on the
production cross section, consistent with the Standard Model: 10.1 pb for the
t-channel, 13.6 pb for the s-channel and 17.8 pb for the combined cross section
of t- and s-channel.Comment: 7 pages, 2 figures, accepted by Phys. Rev.
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