Vanadium Inhalation in a Mouse Model for the Understanding of Air-Suspended Particle Systemic Repercussion

There is an increased concern about the health effects that air-suspended particles have on human health which have been dissected in animal models. Using CD-1 mouse, we explore the effects that vanadium inhalation produce in different tissues and organs. Our findings support the systemic effects of air pollution. In this paper, we describe our findings in different organs in our conditions and contrast our results with the literature

Anisotropy and chemical composition of ultra-high energy cosmic rays using arrival directions measured by the Pierre Auger Observatory

The Pierre Auger Collaboration has reported evidence for anisotropy in the distribution of arrival directions of the cosmic rays with energies $E>E_{th}=5.5\times 10^{19}$ eV. These show a correlation with the distribution of nearby extragalactic objects, including an apparent excess around the direction of Centaurus A. If the particles responsible for these excesses at $E>E_{th}$ are heavy nuclei with charge $Z$, the proton component of the sources should lead to excesses in the same regions at energies $E/Z$. We here report the lack of anisotropies in these directions at energies above $E_{th}/Z$ (for illustrative values of $Z=6,\ 13,\ 26$). If the anisotropies above $E_{th}$ are due to nuclei with charge $Z$, and under reasonable assumptions about the acceleration process, these observations imply stringent constraints on the allowed proton fraction at the lower energies

Update on the correlation of the highest energy cosmic rays with nearby extragalactic matter

Data collected by the Pierre Auger Observatory through 31 August 2007 showed evidence for anisotropy in the arrival directions of cosmic rays above the Greisen-Zatsepin-Kuz'min energy threshold, \nobreak{$6\times 10^{19}$eV}. The anisotropy was measured by the fraction of arrival directions that are less than $3.1^\circ$ from the position of an active galactic nucleus within 75 Mpc (using the V\'eron-Cetty and V\'eron $12^{\rm th}$ catalog). An updated measurement of this fraction is reported here using the arrival directions of cosmic rays recorded above the same energy threshold through 31 December 2009. The number of arrival directions has increased from 27 to 69, allowing a more precise measurement. The correlating fraction is $(38^{+7}_{-6})$, compared with $21$ expected for isotropic cosmic rays. This is down from the early estimate of $(69^{+11}_{-13})$. The enlarged set of arrival directions is examined also in relation to other populations of nearby extragalactic objects: galaxies in the 2 Microns All Sky Survey and active galactic nuclei detected in hard X-rays by the Swift Burst Alert Telescope. A celestial region around the position of the radiogalaxy Cen A has the largest excess of arrival directions relative to isotropic expectations. The 2-point autocorrelation function is shown for the enlarged set of arrival directions and compared to the isotropic expectation.Comment: Accepted for publication in Astroparticle Physics on 31 August 201

Advanced functionality for radio analysis in the Offline software framework of the Pierre Auger Observatory

The advent of the Auger Engineering Radio Array (AERA) necessitates the development of a powerful framework for the analysis of radio measurements of cosmic ray air showers. As AERA performs "radio-hybrid" measurements of air shower radio emission in coincidence with the surface particle detectors and fluorescence telescopes of the Pierre Auger Observatory, the radio analysis functionality had to be incorporated in the existing hybrid analysis solutions for fluoresence and surface detector data. This goal has been achieved in a natural way by extending the existing Auger Offline software framework with radio functionality. In this article, we lay out the design, highlights and features of the radio extension implemented in the Auger Offline framework. Its functionality has achieved a high degree of sophistication and offers advanced features such as vectorial reconstruction of the electric field, advanced signal processing algorithms, a transparent and efficient handling of FFTs, a very detailed simulation of detector effects, and the read-in of multiple data formats including data from various radio simulation codes. The source code of this radio functionality can be made available to interested parties on request.Comment: accepted for publication in NIM A, 13 pages, minor corrections to author list and references in v

Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts infectivity and fusogenicity

The SARS-CoV-2 Omicron BA.1 variant emerged in 2021(1) and has multiple mutations in its spike protein(2). Here we show that the spike protein of Omicron has a higher affinity for ACE2 compared with Delta, and a marked change in its antigenicity increases Omicron's evasion of therapeutic monoclonal and vaccine-elicited polyclonal neutralizing antibodies after two doses. mRNA vaccination as a third vaccine dose rescues and broadens neutralization. Importantly, the antiviral drugs remdesivir and molnupiravir retain efficacy against Omicron BA.1. Replication was similar for Omicron and Delta virus isolates in human nasal epithelial cultures. However, in lung cells and gut cells, Omicron demonstrated lower replication. Omicron spike protein was less efficiently cleaved compared with Delta. The differences in replication were mapped to the entry efficiency of the virus on the basis of spike-pseudotyped virus assays. The defect in entry of Omicron pseudotyped virus to specific cell types effectively correlated with higher cellular RNA expression of TMPRSS2, and deletion of TMPRSS2 affected Delta entry to a greater extent than Omicron. Furthermore, drug inhibitors targeting specific entry pathways(3) demonstrated that the Omicron spike inefficiently uses the cellular protease TMPRSS2, which promotes cell entry through plasma membrane fusion, with greater dependency on cell entry through the endocytic pathway. Consistent with suboptimal S1/S2 cleavage and inability to use TMPRSS2, syncytium formation by the Omicron spike was substantially impaired compared with the Delta spike. The less efficient spike cleavage of Omicron at S1/S2 is associated with a shift in cellular tropism away from TMPRSS2-expressing cells, with implications for altered pathogenesis

Search for First Harmonic Modulation in the Right Ascension Distribution of Cosmic Rays Detected at the Pierre Auger Observatory

We present the results of searches for dipolar-type anisotropies in different energy ranges above $2.5\times 10^{17}$ eV with the surface detector array of the Pierre Auger Observatory, reporting on both the phase and the amplitude measurements of the first harmonic modulation in the right-ascension distribution. Upper limits on the amplitudes are obtained, which provide the most stringent bounds at present, being below 2% at 99% $C.L.$ for EeV energies. We also compare our results to those of previous experiments as well as with some theoretical expectations.Comment: 28 pages, 11 figure

Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts infectivity and fusogenicity

The SARS-CoV-2 Omicron BA.1 variant emerged in 20211 and has multiple mutations in its spike protein2. Here we show that the spike protein of Omicron has a higher affinity for ACE2 compared with Delta, and a marked change in its antigenicity increases Omicron’s evasion of therapeutic monoclonal and vaccine-elicited polyclonal neutralizing antibodies after two doses. mRNA vaccination as a third vaccine dose rescues and broadens neutralization. Importantly, the antiviral drugs remdesivir and molnupiravir retain efficacy against Omicron BA.1. Replication was similar for Omicron and Delta virus isolates in human nasal epithelial cultures. However, in lung cells and gut cells, Omicron demonstrated lower replication. Omicron spike protein was less efficiently cleaved compared with Delta. The differences in replication were mapped to the entry efficiency of the virus on the basis of spike-pseudotyped virus assays. The defect in entry of Omicron pseudotyped virus to specific cell types effectively correlated with higher cellular RNA expression of TMPRSS2, and deletion of TMPRSS2 affected Delta entry to a greater extent than Omicron. Furthermore, drug inhibitors targeting specific entry pathways3 demonstrated that the Omicron spike inefficiently uses the cellular protease TMPRSS2, which promotes cell entry through plasma membrane fusion, with greater dependency on cell entry through the endocytic pathway. Consistent with suboptimal S1/S2 cleavage and inability to use TMPRSS2, syncytium formation by the Omicron spike was substantially impaired compared with the Delta spike. The less efficient spike cleavage of Omicron at S1/S2 is associated with a shift in cellular tropism away from TMPRSS2-expressing cells, with implications for altered pathogenesis

Using C. elegans to discover therapeutic compounds for ageing-associated neurodegenerative diseases

Age-associated neurodegenerative disorders such as Alzheimer’s disease are a major public health challenge, due to the demographic increase in the proportion of older individuals in society. However, the relatively few currently approved drugs for these conditions provide only symptomatic relief. A major goal of neurodegeneration research is therefore to identify potential new therapeutic compounds that can slow or even reverse disease progression, either by impacting directly on the neurodegenerative process or by activating endogenous physiological neuroprotective mechanisms that decline with ageing. This requires model systems that can recapitulate key features of human neurodegenerative diseases that are also amenable to compound screening approaches. Mammalian models are very powerful, but are prohibitively expensive for high-throughput drug screens. Given the highly conserved neurological pathways between mammals and invertebrates, Caenorhabditis elegans has emerged as a powerful tool for neuroprotective compound screening. Here we describe how C. elegans has been used to model various human ageing-associated neurodegenerative diseases and provide an extensive list of compounds that have therapeutic activity in these worm models and so may have translational potential