384 research outputs found
Rcor2 underexpression in senescent mice: a target for inflammaging?
BACKGROUND: Aging is characterized by a low-grade systemic inflammation that contributes to the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). However, little knowledge is currently available on the molecular processes leading to chronic neuroinflammation. In this context, recent studies have described the role of chromatin regulators in inflammation and longevity including the REST corepressor (Rcor)-2 factor, which seems to be involved in an inflammatory suppressive program. METHODS: To assess the impact of Rcor2 in age-related inflammation, gene expression levels were quantified in different tissues and ages of the spontaneous senescence-accelerated P8 mouse (P8) using the SAMR1 mouse (R1) as a control. Specific siRNA transfection in P8 and R1 astrocyte cultures was used to determine Rcor2 involvement in the modulation of neuroinflammation. The effect of lipopolysaccharide (LPS) treatment on Rcor2 levels and neuroinflammation was analyzed both in vivo and in vitro. RESULTS: P8 mice presented a dramatic decrease in Rcor2 gene expression compared with R1 controls in splenocytes, an alteration also observed in the brain cortex, hippocampus and primary astrocytes of these mice. Rcor2 reduction in astrocytes was accompanied by an increased basal expression of the interleukin (Il)-6 gene. Strikingly, intraperitoneal LPS injection in R1 mice downregulated Rcor2 in the hippocampus, with a concomitant upregulation of tumor necrosis factor (Tnf-α), Il1-β and Il6 genes. A negative correlation between Rcor2 and Il6 gene expression was also verified in LPS-treated C6 glioma cells. Knock down of Rcor2 by siRNA transfection (siRcor2) in R1 astrocytes upregulated Il6 gene expression while siRcor2 further increased Il6 expression in P8 astrocytes. Moreover, LPS activation provoked a further downregulation of Rcor2 and an amplified induction of Il6 in siRcor2-tranfected astrocytes. CONCLUSIONS: Data presented here show interplay between Rcor2 downregulation and increased inflammation and suggest that Rcor2 may be a key regulator of inflammagin
Eradication of bovine tuberculosis at a herd-level in Madrid, Spain: study of within-herd transmission dynamics over a 12 year period
BACKGROUND
Eradication of bovine tuberculosis (bTB) through the application of test-and-cull programs is a declared goal of developed countries in which the disease is still endemic. Here, longitudinal data from more than 1,700 cattle herds tested during a 12 year-period in the eradication program in the region of Madrid, Spain, were analyzed to quantify the within-herd transmission coefficient (β) depending on the herd-type (beef/dairy/bullfighting). In addition, the probability to recover the officially bTB free (OTF) status in infected herds depending on the type of herd and the diagnostic strategy implemented was assessed using Cox proportional hazard models.
RESULTS
Overall, dairy herds showed higher β (median 4.7) than beef or bullfighting herds (2.3 and 2.2 respectively). Introduction of interferon-gamma (IFN-γ) as an ancillary test produced an apparent increase in the β coefficient regardless of production type, likely due to an increase in diagnostic sensitivity. Time to recover OTF status was also significantly lower in dairy herds, and length of bTB episodes was significantly reduced when the IFN-γ was implemented to manage the outbreak.
CONCLUSIONS
Our results suggest that bTB spreads more rapidly in dairy herds compared to other herd types, a likely cause being management and demographic-related factors. However, outbreaks in dairy herds can be controlled more rapidly than in typically extensive herd types. Finally, IFN-γ proved its usefulness to rapidly eradicate bTB at a herd-level
Constraining the Ratio in TeV Cosmic Rays with Observations of the Moon Shadow by HAWC
An indirect measurement of the antiproton flux in cosmic rays is possible as
the particles undergo deflection by the geomagnetic field. This effect can be
measured by studying the deficit in the flux, or shadow, created by the Moon as
it absorbs cosmic rays that are headed towards the Earth. The shadow is
displaced from the actual position of the Moon due to geomagnetic deflection,
which is a function of the energy and charge of the cosmic rays. The
displacement provides a natural tool for momentum/charge discrimination that
can be used to study the composition of cosmic rays. Using 33 months of data
comprising more than 80 billion cosmic rays measured by the High Altitude Water
Cherenkov (HAWC) observatory, we have analyzed the Moon shadow to search for
TeV antiprotons in cosmic rays. We present our first upper limits on the
fraction, which in the absence of any direct measurements, provide
the tightest available constraints of on the antiproton fraction for
energies between 1 and 10 TeV.Comment: 10 pages, 5 figures. Accepted by Physical Review
VAMOS: a Pathfinder for the HAWC Gamma-Ray Observatory
VAMOS was a prototype detector built in 2011 at an altitude of 4100m a.s.l.
in the state of Puebla, Mexico. The aim of VAMOS was to finalize the design,
construction techniques and data acquisition system of the HAWC observatory.
HAWC is an air-shower array currently under construction at the same site of
VAMOS with the purpose to study the TeV sky. The VAMOS setup included six water
Cherenkov detectors and two different data acquisition systems. It was in
operation between October 2011 and May 2012 with an average live time of 30%.
Besides the scientific verification purposes, the eight months of data were
used to obtain the results presented in this paper: the detector response to
the Forbush decrease of March 2012, and the analysis of possible emission, at
energies above 30 GeV, for long gamma-ray bursts GRB111016B and GRB120328B.Comment: Accepted for pubblication in Astroparticle Physics Journal (20 pages,
10 figures). Corresponding authors: A.Marinelli and D.Zaboro
Women with psychotic episodes during pregnancy show increased markers of placental damage with Tenney-Parker changes
y. Psychosis is a hazardous and functionally
disruptive psychiatric condition which may affect
women in pregnancy, entailing negative consequences
for maternofetal well-being. The precise pathophysiological basis and consequences of a psychotic episode in
pregnancy remain to be further elucidated. The placenta
is a pivotal tissue with many functions in the gestational
period, critically influencing the fate and development of
pregnancy. Although detrimental alterations have been
observed in women undergoing severe psychiatric
disorders in pregnancy, there are little studies evaluating
the consequences of suffering from a psychotic episode
in the placental tissue In this work, we have evaluated
the histopathological consequences of a first episode of
psychosis in pregnancy (FE-PW; N=22) and compare
them with healthy pregnant women (HC-PW; N=20) by
using histological, immunohistochemical and gene
expression techniques. Our results define that the
placental tissue of FE-PW display an increase in the
number of placental villi, bridges, syncytial knots and
syncytial knots/villi. Besides, we have also observed an
enhanced gene and protein expression in FE-PW of the
hypoxic marker HIF-1α, together with the apoptotic
markers BAX and Bcl-2. To our knowledge, this is the
first study demonstrating significant histopathological
changes in the placenta of women suffering a new-onset
psychotic episode in pregnancy. Further studies should
be aimed at deepening the knowledge about the
pernicious effects of psychosis in the maternofetal
tissues, as well as the potential implications of these
alterations
Observation of the Crab Nebula with the HAWC Gamma-Ray Observatory
The Crab Nebula is the brightest TeV gamma-ray source in the sky and has been
used for the past 25 years as a reference source in TeV astronomy, for
calibration and verification of new TeV instruments. The High Altitude Water
Cherenkov Observatory (HAWC), completed in early 2015, has been used to observe
the Crab Nebula at high significance across nearly the full spectrum of
energies to which HAWC is sensitive. HAWC is unique for its wide field-of-view,
nearly 2 sr at any instant, and its high-energy reach, up to 100 TeV. HAWC's
sensitivity improves with the gamma-ray energy. Above 1 TeV the
sensitivity is driven by the best background rejection and angular resolution
ever achieved for a wide-field ground array.
We present a time-integrated analysis of the Crab using 507 live days of HAWC
data from 2014 November to 2016 June. The spectrum of the Crab is fit to a
function of the form . The data is well-fit with values of
, , and
log when
is fixed at 7 TeV and the fit applies between 1 and 37 TeV. Study of the
systematic errors in this HAWC measurement is discussed and estimated to be
50\% in the photon flux between 1 and 37 TeV.
Confirmation of the Crab flux serves to establish the HAWC instrument's
sensitivity for surveys of the sky. The HAWC survey will exceed sensitivity of
current-generation observatories and open a new view of 2/3 of the sky above 10
TeV.Comment: Submitted 2017/01/06 to the Astrophysical Journa
All-particle cosmic ray energy spectrum measured by the HAWC experiment from 10 to 500 TeV
We report on the measurement of the all-particle cosmic ray energy spectrum
with the High Altitude Water Cherenkov (HAWC) Observatory in the energy range
10 to 500 TeV. HAWC is a ground based air-shower array deployed on the slopes
of Volcan Sierra Negra in the state of Puebla, Mexico, and is sensitive to
gamma rays and cosmic rays at TeV energies. The data used in this work were
taken from 234 days between June 2016 to February 2017. The primary cosmic-ray
energy is determined with a maximum likelihood approach using the particle
density as a function of distance to the shower core. Introducing quality cuts
to isolate events with shower cores landing on the array, the reconstructed
energy distribution is unfolded iteratively. The measured all-particle spectrum
is consistent with a broken power law with an index of prior to
a break at ) TeV, followed by an index of . The
spectrum also respresents a single measurement that spans the energy range
between direct detection and ground based experiments. As a verification of the
detector response, the energy scale and angular resolution are validated by
observation of the cosmic ray Moon shadow's dependence on energy.Comment: 16 pages, 11 figures, 4 tables, submission to Physical Review
Measurement of the Crab Nebula Spectrum Past 100 TeV with HAWC
We present TeV gamma-ray observations of the Crab Nebula, the standard
reference source in ground-based gamma-ray astronomy, using data from the High
Altitude Water Cherenkov (HAWC) Gamma-Ray Observatory. In this analysis we use
two independent energy-estimation methods that utilize extensive air shower
variables such as the core position, shower angle, and shower lateral energy
distribution. In contrast, the previously published HAWC energy spectrum
roughly estimated the shower energy with only the number of photomultipliers
triggered. This new methodology yields a much improved energy resolution over
the previous analysis and extends HAWC's ability to accurately measure
gamma-ray energies well beyond 100 TeV. The energy spectrum of the Crab Nebula
is well fit to a log parabola shape with emission up to at least 100 TeV. For the first
estimator, a ground parameter that utilizes fits to the lateral distribution
function to measure the charge density 40 meters from the shower axis, the
best-fit values are
=(2.350.04)10 (TeV cm
s), =2.790.02, and
=0.100.01. For the second estimator, a neural
network which uses the charge distribution in annuli around the core and other
variables, these values are
=(2.310.02)10 (TeV cm
s), =2.730.02, and
=0.060.010.02. The first set of uncertainties are statistical;
the second set are systematic. Both methods yield compatible results. These
measurements are the highest-energy observation of a gamma-ray source to date.Comment: published in Ap
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