1,753 research outputs found
Long-term treatment with chloroquine increases lifespan in middle-aged male mice possibly via autophagy modulation, proteasome inhibition and glycogen metabolism
Previous studies have shown that the polyamine spermidine increased the maximum life span in C. elegans and the median life span in mice. Since spermidine increases autophagy, we asked if treatment with chloroquine, an inhibitor of autophagy, would shorten the lifespan of mice. Recently, chloroquine has intensively been discussed as a treatment option for COVID-19 patients. To rule out unfavorable long-term effects on longevity, we examined the effect of chronic treatment with chloroquine given in the drinking water on the lifespan and organ pathology of male middle-aged NMRI mice. We report that, surprisingly, daily treatment with chloroquine extended the median life span by 11.4% and the maximum life span of the middle-aged male NMRI mice by 11.8%. Subsequent experiments show that the chloroquine-induced lifespan elevation is associated with dose-dependent increase in LC3B-II, a marker of autophagosomes, in the liver and heart that was confirmed by transmission electron microscopy. Quite intriguingly, chloroquine treatment was also associated with a decrease in glycogenolysis in the liver suggesting a compensatory mechanism to provide energy to the cell. Accumulation of autophagosomes was paralleled by an inhibition of proteasome-dependent proteolysis in the liver and the heart as well as with decreased serum levels of insulin growth factor binding protein-3 (IGFBP3), a protein associated with longevity. We propose that inhibition of proteasome activity in conjunction with an increased number of autophagosomes and decreased levels of IGFBP3 might play a central role in lifespan extension by chloroquine in male NMRI mice.UEFISCDI (EU Horizon 2020 Research and Innovation Programme), Consiliul National al Cercetarii Stiintifice (CNCS), Unitatea Executiva pentru Finantarea Invatamantului Superior, a Cercetarii, Dezvoltarii si Inovarii (UEFISCDI
Search for muon-neutrino emission from GeV and TeV gamma-ray flaring blazars using five years of data of the ANTARES telescope
The ANTARES telescope is well-suited for detecting astrophysical transient
neutrino sources as it can observe a full hemisphere of the sky at all times
with a high duty cycle. The background due to atmospheric particles can be
drastically reduced, and the point-source sensitivity improved, by selecting a
narrow time window around possible neutrino production periods. Blazars, being
radio-loud active galactic nuclei with their jets pointing almost directly
towards the observer, are particularly attractive potential neutrino point
sources, since they are among the most likely sources of the very high-energy
cosmic rays. Neutrinos and gamma rays may be produced in hadronic interactions
with the surrounding medium. Moreover, blazars generally show high time
variability in their light curves at different wavelengths and on various time
scales. This paper presents a time-dependent analysis applied to a selection of
flaring gamma-ray blazars observed by the FERMI/LAT experiment and by TeV
Cherenkov telescopes using five years of ANTARES data taken from 2008 to 2012.
The results are compatible with fluctuations of the background. Upper limits on
the neutrino fluence have been produced and compared to the measured gamma-ray
spectral energy distribution.Comment: 27 pages, 16 figure
Granulocyte-colony stimulating factor (G-CSF) for stroke: an individual patient data meta-analysis
Granulocyte colony stimulating factor (G-CSF) may enhance recovery from stroke through neuroprotective mechanisms if administered early, or neurorepair if given later. Several small trials suggest administration is safe but effects on efficacy are unclear. We searched for randomised controlled trials (RCT) assessing G-CSF in patients with hyperacute, acute, subacute or chronic stroke, and asked Investigators to share individual patient data on baseline characteristics, stroke severity and type, end-of trial modified Rankin Scale (mRS), Barthel Index, haematological parameters, serious adverse events and death. Multiple variable analyses were adjusted for age, sex, baseline severity and time-to-treatment. Individual patient data were obtained for 6 of 10 RCTs comprising 196 stroke patients (116 G-CSF, 80 placebo), mean age 67.1 (SD 12.9), 92% ischaemic, median NIHSS 10 (IQR 5-15), randomised 11 days (interquartile range IQR 4-238) post ictus; data from three commercial trials were not shared. G-CSF did not improve mRS (ordinal regression), odds ratio OR 1.12 (95% confidence interval 0.64 to 1.96, p=0.62). There were more patients with a serious adverse event in the G-CSF group (29.6% versus 7.5%, p=0.07) with no significant difference in all-cause mortality (G-CSF 11.2%, placebo 7.6%, p=0.4). Overall, G-CSF did not improve stroke outcome in this individual patient data meta-analysis
The Antares Collaboration : Contributions to the 34th International Cosmic Ray Conference (ICRC 2015, The Hague)
The ANTARES detector, completed in 2008, is the largest neutrino telescope in the Northern hemisphere. Located at a depth of 2.5 km in the Mediterranean Sea, 40 km off the Toulon shore, its main goal is the search for astrophysical high energy neutrinos. In this paper we collect the 21 contributions of the ANTARES collaboration to the 34th International Cosmic Ray Conference (ICRC 2015). The scientific output is very rich and the contributions included in these proceedings cover the main physics results, ranging from steady point sources, diffuse searches, multi-messenger analyses to exotic physics
Monomeric C-reactive protein-a key molecule driving development of Alzheimer's disease associated with brain ischaemia?
Alzheimer’s disease (AD) increases dramatically in patients with ischaemic stroke. Monomeric
C-reactive protein (mCRP) appears in the ECM of ischaemic tissue after stroke, associating with
microvasculature, neurons and AD-plaques, Aβ, also, being able to dissociate native-CRP into
inflammatory, mCRP in vivo. Here, mCRP injected into the hippocampal region of mice was
retained within the retrosplenial tract of the dorsal 3rd ventrical and surrounding major vessels.
Mice developed behavioural/cognitive deficits within 1 month, concomitant with mCRP staining
within abnormal looking neurons expressing p-tau and in beta-amyloid 1-42-plaque positive regions.
mCRP co-localised with CD105 in microvessels suggesting angiogenesis. Phospho-arrays/Western
blotting identified signalling activation in endothelial cells and neurons through p-IRS-1, p-Tau and
p-ERK1/2-which was blocked following pre-incubation with mCRP-antibody. mCRP increased vascular
monolayer permeability and gap junctions, increased NCAM expression and produced haemorrhagic
angiogenesis in mouse matrigel implants. mCRP induced tau244–372 aggregation and assembly in
vitro. IHC study of human AD/stroke patients revealed co-localization of mCRP with Aβ plaques,
tau-like fibrils and IRS-1/P-Tau positive neurons and high mCRP-levels spreading from infarcted core
regions matched reduced expression of Aβ/Tau. mCRP may be responsible for promoting dementia
after ischaemia and mCRP clearance could inform therapeutic avenues to reduce the risk of future dementia
A First Search for coincident Gravitational Waves and High Energy Neutrinos using LIGO, Virgo and ANTARES data from 2007
We present the results of the first search for gravitational wave bursts
associated with high energy neutrinos. Together, these messengers could reveal
new, hidden sources that are not observed by conventional photon astronomy,
particularly at high energy. Our search uses neutrinos detected by the
underwater neutrino telescope ANTARES in its 5 line configuration during the
period January - September 2007, which coincided with the fifth and first
science runs of LIGO and Virgo, respectively. The LIGO-Virgo data were analysed
for candidate gravitational-wave signals coincident in time and direction with
the neutrino events. No significant coincident events were observed. We place
limits on the density of joint high energy neutrino - gravitational wave
emission events in the local universe, and compare them with densities of
merger and core-collapse events.Comment: 19 pages, 8 figures, science summary page at
http://www.ligo.org/science/Publication-S5LV_ANTARES/index.php. Public access
area to figures, tables at
https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=p120000
Attenuated Inflammatory Response in Aged Mice Brains following Stroke
Background: Increased age is a major risk factor for stroke incidence, post-ischemic mortality, and severe and long-term disability. Stroke outcome is considerably influenced by post-ischemic mechanisms. We hypothesized that the inflammatory response following an ischemic injury is altered in aged organisms. Methods and Results: To that end, we analyzed the expression pattern of pro-inflammatory cytokines (TNF, IL-1a, IL-1b, IL-6), anti-inflammatory cytokines (IL-10, TGFb1), and chemokines (Mip-1a, MCP-1, RANTES) of adult (2 months) and aged (24 months) mice brains at different reperfusion times (6 h, 12 h, 24 h, 2 d, 7 d) following transient occlusion of the middle cerebral artery. The infarct size was assessed to monitor possible consequences of an altered inflammatory response in aged mice. Our data revealed an increased neuro-inflammation with age. Above all, we found profound age-related alterations in the reaction to stroke. The response of pro-inflammatory cytokines (TNF, and IL-1b) and the level of chemokines (Mip-1a, and MCP-1) were strongly diminished in the aged post-ischemic brain tissue. IL-6 showed the strongest age-dependent decrease in its post-ischemic expression profile. Anti-inflammatory cytokines (TGFb1, and IL-10) revealed no significant age dependency after ischemia. Aged mice brains tend to develop smaller infarcts. Conclusion: The attenuated inflammatory response to stroke in aged animals may contribute to their smaller infarcts. The results presented here highlight the importance of using aged animals to investigate age-associated diseases like stroke
Status and Recent Results of the Acoustic Neutrino Detection Test System AMADEUS
The AMADEUS system is an integral part of the ANTARES neutrino telescope in
the Mediterranean Sea. The project aims at the investigation of techniques for
acoustic neutrino detection in the deep sea. Installed at a depth of more than
2000m, the acoustic sensors of AMADEUS are based on piezo-ceramics elements for
the broad-band recording of signals with frequencies ranging up to 125kHz.
AMADEUS was completed in May 2008 and comprises six "acoustic clusters", each
one holding six acoustic sensors that are arranged at distances of roughly 1m
from each other. The clusters are installed with inter-spacings ranging from
15m to 340m. Acoustic data are continuously acquired and processed at a
computer cluster where online filter algorithms are applied to select a
high-purity sample of neutrino-like signals. 1.6 TB of data were recorded in
2008 and 3.2 TB in 2009. In order to assess the background of neutrino-like
signals in the deep sea, the characteristics of ambient noise and transient
signals have been investigated. In this article, the AMADEUS system will be
described and recent results will be presented.Comment: 7 pages, 8 figures. Proceedings of ARENA 2010, the 4th International
Workshop on Acoustic and Radio EeV Neutrino Detection Activitie
Measurement of Atmospheric Neutrino Oscillations with the ANTARES Neutrino Telescope
The data taken with the ANTARES neutrino telescope from 2007 to 2010, a total
live time of 863 days, are used to measure the oscillation parameters of
atmospheric neutrinos. Muon tracks are reconstructed with energies as low as 20
GeV. Neutrino oscillations will cause a suppression of vertical upgoing muon
neutrinos of such energies crossing the Earth. The parameters determining the
oscillation of atmospheric neutrinos are extracted by fitting the event rate as
a function of the ratio of the estimated neutrino energy and reconstructed
flight path through the Earth. Measurement contours of the oscillation
parameters in a two-flavour approximation are derived. Assuming maximum mixing,
a mass difference of eV is
obtained, in good agreement with the world average value.Comment: 9 pages, 5 figure
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