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 pˉ/p\bar{p}/p 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 $\bar{p}/p$ fraction, which in the absence of any direct measurements, provide the tightest available constraints of $\sim1\%$ 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 $\sim$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 $\phi(E) = \phi_0 (E/E_{0})^{-\alpha -\beta\cdot{\rm{ln}}(E/E_{0})}$. The data is well-fit with values of $\alpha=2.63\pm0.03$, $\beta=0.15\pm0.03$, and log$_{10}(\phi_0~{\rm{cm}^2}~{\rm{s}}~{\rm{TeV}})=-12.60\pm0.02$ when $E_{0}$ 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 $\pm$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 $-2.49\pm0.01$ prior to a break at $(45.7\pm0.1$) TeV, followed by an index of $-2.71\pm0.01$. 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 $\left(\frac{dN}{dE} = \phi_0 \left(E/\textrm{7 TeV}\right)^{-\alpha-\beta\ln\left(E/\textrm{7 TeV}\right)}\right)$ 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 $\phi_o$=(2.35$\pm$0.04$^{+0.20}_{-0.21}$)$\times$10$^{-13}$ (TeV cm$^2$ s)$^{-1}$, $\alpha$=2.79$\pm$0.02$^{+0.01}_{-0.03}$, and $\beta$=0.10$\pm$0.01$^{+0.01}_{-0.03}$. For the second estimator, a neural network which uses the charge distribution in annuli around the core and other variables, these values are $\phi_o$=(2.31$\pm$0.02$^{+0.32}_{-0.17}$)$\times$10$^{-13}$ (TeV cm$^2$ s)$^{-1}$, $\alpha$=2.73$\pm$0.02$^{+0.03}_{-0.02}$, and $\beta$=0.06$\pm$0.01$\pm$0.02. 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