Il10 Deficiency Rebalances Innate Immunity to Mitigate Alzheimer-Like Pathology

SummaryThe impact of inflammation suppressor pathways on Alzheimer’s disease (AD) evolution remains poorly understood. Human genetic evidence suggests involvement of the cardinal anti-inflammatory cytokine, interleukin-10 (IL10). We crossed the APP/PS1 mouse model of cerebral amyloidosis with a mouse deficient in Il10 (APP/PS1+Il10−/−). Quantitative in silico 3D modeling revealed activated Aβ phagocytic microglia in APP/PS1+Il10−/− mice that restricted cerebral amyloidosis. Genome-wide RNA sequencing of APP/PS1+Il10−/− brains showed selective modulation of innate immune genes that drive neuroinflammation. Il10 deficiency preserved synaptic integrity and mitigated cognitive disturbance in APP/PS1 mice. In vitro knockdown of microglial Il10-Stat3 signaling endorsed Aβ phagocytosis, while exogenous IL-10 had the converse effect. Il10 deficiency also partially overcame inhibition of microglial Aβ uptake by human Apolipoprotein E. Finally, the IL-10 signaling pathway was abnormally elevated in AD patient brains. Our results suggest that “rebalancing” innate immunity by blocking the IL-10 anti-inflammatory response may be therapeutically relevant for AD

USE OF RECYCLED PLASTIC AS REPLACEMENT OF FINE AGGREGATE IN STRUCTURAL CONCRETE

Now a days disposal of dissipate plastic is one of the major green problem all above the world. The objective of this review paper is to examine the usefulness of using waste plastic as fine aggregate substitute in concrete mixtures. The compressive and tensile strength of a variety of concrete specimens were tested to establish how the amalgamation of recycled plastic as a replacement of fine aggregate would affect the expansion of strength in the mixes. In this reading plastic waste was mixed with cement concrete in a variety of scope such as 0%-15% and the M20 grade test specimen were casted to learning the behavior of plastic mixed concrete. All stages of plastic replacement show a perceptible diminish in compressive strength and tensile strength. https://journalnx.com/journal-article/2015071

Introduction of human papillomavirus (HPV) vaccination into national immunisation schedules in Europe: Results of the VENICE 2007 survey

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Prevalence and pathogenic diversity in pearl millet downy mildew pathogen populations in Maharashtra, India

Pearl millet fields were surveyed in Maharashtra, India during the rainy seasons of 2009 and 2010 to monitor onfarm downy mildew (DM) incidence and assess the pathogenic diversity among native populations of Sclerospora graminicola. Of the 131 fields surveyed in seven districts in Maharashtra, DM was observed in 72 fields in the range of 1–90%. DM was quite severe in Ahmednagar, Jalgaon, Aurangabad and Jalna districts with mean disease incidence of 56, 40, 35 and 32, respectively. Severe DM was observed on Pioneer 86M32, B 2301, GK 419, Tulsi, 535, 452 and several hybrids of unknown identity; whereas hybrids MRB 204, Nirmal 40, Sathya, Super 515, Super Boss, Tulja, XL 51, Great 555, Nuzvid 2301, Paras 51 and Sandeep were free from DM. Twenty six S. graminicola isolates collected during 2009–10 from Maharashtra were evaluated for pathogenic diversity on seven pearl millet host differential lines along with three isolates of S. graminicola collected earlier from the same region. Mean disease incidence on host differentials varied from 5 to 80%. S. graminicola isolates Sg 542, Sg 543, Sg 544, Sg 545, Sg 547, Sg 549, Sg 550, Sg 552, Sg 553, Sg 554 and Sg 555 showed > 50% mean DM incidence across host differentials. Highly virulent isolate Sg 542 collected from Deogaon, Aurangabad has been selected for the greenhouse screening of pearl millet lines being developed for Maharashtr

The social geography of unmarried cohabitation in the USA, 2007-2011

US studies of marriage and cohabitation have mainly highlighted the social and racial differentials as they were observed in cross-sections, and have as a result essentially focused on the "pattern of disadvantage". The evolution of such social differentials over time and space reveals that this pattern of disadvantage has clearly persisted, but that it is far from covering the whole story. Historically, there has been a major contribution to the rise of cohabitation by white college students, and later on young white adults with higher education continued to start unions via cohabitation to ever increasing degrees. Only, they seem to move into marriage to a greater extent later on in life than other population segments. Also, the religious affiliation matters greatly: Mormons and evangelical Christians have resisted the current trends. Furthermore this effect is not only operating at the individual but at the contextual level as well. Conversely, even after controls for competing socio-economic explanations, residence in areas (either counties or PUMA-areas) with a Democratic voting pattern is related to higher cohabitation probabilities. And, finally, different legal contexts at the level of States also significantly contributed to the emergence of strong spatial contrasts. Hence, there is a concurrence of several factors shaping the present differentiations, and the rise of secular and liberal attitudes, i.e. the "ethics revolution", is equally a part of the explanation

Genetic determinants of co-accessible chromatin regions in activated T cells across humans.

Over 90% of genetic variants associated with complex human traits map to non-coding regions, but little is understood about how they modulate gene regulation in health and disease. One possible mechanism is that genetic variants affect the activity of one or more cis-regulatory elements leading to gene expression variation in specific cell types. To identify such cases, we analyzed ATAC-seq and RNA-seq profiles from stimulated primary CD4+ T cells in up to 105 healthy donors. We found that regions of accessible chromatin (ATAC-peaks) are co-accessible at kilobase and megabase resolution, consistent with the three-dimensional chromatin organization measured by in situ Hi-C in T cells. Fifteen percent of genetic variants located within ATAC-peaks affected the accessibility of the corresponding peak (local-ATAC-QTLs). Local-ATAC-QTLs have the largest effects on co-accessible peaks, are associated with gene expression and are enriched for autoimmune disease variants. Our results provide insights into how natural genetic variants modulate cis-regulatory elements, in isolation or in concert, to influence gene expression

A search for point sources of EeV photons

Measurements of air showers made using the hybrid technique developed with the fluorescence and surface detectors of the Pierre Auger Observatory allow a sensitive search for point sources of EeV photons anywhere in the exposed sky. A multivariate analysis reduces the background of hadronic cosmic rays. The search is sensitive to a declination band from -85{\deg} to +20{\deg}, in an energy range from 10^17.3 eV to 10^18.5 eV. No photon point source has been detected. An upper limit on the photon flux has been derived for every direction. The mean value of the energy flux limit that results from this, assuming a photon spectral index of -2, is 0.06 eV cm^-2 s^-1, and no celestial direction exceeds 0.25 eV cm^-2 s^-1. These upper limits constrain scenarios in which EeV cosmic ray protons are emitted by non-transient sources in the Galaxy.Comment: 28 pages, 10 figures, accepted for publication in The Astrophysical Journa

Reconstruction of inclined air showers detected with the Pierre Auger Observatory

We describe the method devised to reconstruct inclined cosmic-ray air showers with zenith angles greater than $60^\circ$ detected with the surface array of the Pierre Auger Observatory. The measured signals at the ground level are fitted to muon density distributions predicted with atmospheric cascade models to obtain the relative shower size as an overall normalization parameter. The method is evaluated using simulated showers to test its performance. The energy of the cosmic rays is calibrated using a sub-sample of events reconstructed with both the fluorescence and surface array techniques. The reconstruction method described here provides the basis of complementary analyses including an independent measurement of the energy spectrum of ultra-high energy cosmic rays using very inclined events collected by the Pierre Auger Observatory.Comment: 27 pages, 19 figures, accepted for publication in Journal of Cosmology and Astroparticle Physics (JCAP

Azimuthal asymmetry in the risetime of the surface detector signals of the Pierre Auger Observatory

The azimuthal asymmetry in the risetime of signals in Auger surface detector stations is a source of information on shower development. The azimuthal asymmetry is due to a combination of the longitudinal evolution of the shower and geometrical effects related to the angles of incidence of the particles into the detectors. The magnitude of the effect depends upon the zenith angle and state of development of the shower and thus provides a novel observable, $(\sec \theta)_\mathrm{max}$, sensitive to the mass composition of cosmic rays above $3 \times 10^{18}$ eV. By comparing measurements with predictions from shower simulations, we find for both of our adopted models of hadronic physics (QGSJETII-04 and EPOS-LHC) an indication that the mean cosmic-ray mass increases slowly with energy, as has been inferred from other studies. However, the mass estimates are dependent on the shower model and on the range of distance from the shower core selected. Thus the method has uncovered further deficiencies in our understanding of shower modelling that must be resolved before the mass composition can be inferred from $(\sec \theta)_\mathrm{max}$.Comment: Replaced with published version. Added journal reference and DO

The Pierre Auger Observatory: Contributions to the 34th International Cosmic Ray Conference (ICRC 2015)

Contributions of the Pierre Auger Collaboration to the 34th International Cosmic Ray Conference, 30 July - 6 August 2015, The Hague, The NetherlandsComment: 24 proceedings, the 34th International Cosmic Ray Conference, 30 July - 6 August 2015, The Hague, The Netherlands; will appear in PoS(ICRC2015