Pulsar-wind nebulae and magnetar outflows: observations at radio, X-ray, and gamma-ray wavelengths

We review observations of several classes of neutron-star-powered outflows: pulsar-wind nebulae (PWNe) inside shell supernova remnants (SNRs), PWNe interacting directly with interstellar medium (ISM), and magnetar-powered outflows. We describe radio, X-ray, and gamma-ray observations of PWNe, focusing first on integrated spectral-energy distributions (SEDs) and global spectral properties. High-resolution X-ray imaging of PWNe shows a bewildering array of morphologies, with jets, trails, and other structures. Several of the 23 so far identified magnetars show evidence for continuous or sporadic emission of material, sometimes associated with giant flares, and a few possible "magnetar-wind nebulae" have been recently identified.Comment: 61 pages, 44 figures (reduced in quality for size reasons). Published in Space Science Reviews, "Jets and Winds in Pulsar Wind Nebulae, Gamma-ray Bursts and Blazars: Physics of Extreme Energy Release

Data-driven model of the hippocampus using the HBP Brain Simulation Platform

The hippocampus is one of four brain regions being modeled in the ramp-up phase of the Human Brain Project (HBP), testing and guiding the development of the HBP Brain Simulation Platform (BSP) to be released in March 2016. Using preliminary versions of BSP applications developed at the Blue Brain Project, a first draft data-driven model of hippocampus was assembled, integrating data available from HBP and community sources. In brief, the building process started by populating the hippocampal volume, defined by the Allen Brain Atlas, with a series of reconstructions of well-characterized cell types according to experimentally observed densities and proportions. A connectome was generated as previously described [1], constrained by biological values for bouton density and synapses per connection. Single cell electrical models and synapse physiology were constrained by electrophysiological recordings and publicly available data. Further datasets not used as input during model building were used to validate the model. This first draft of the circuit model and the pipeline to build it are to be released with the HBP-BSP in March 2016, and they will be periodically updated. The model represents a resource for the community to integrate data, perform in silico experiments, and test hypotheses. Establishing a community process for the continued refinement of the model is planned for the next phase of the HBP. [1] Reimann, M. et al. An algorithm to predict the connectome of neural microcircuits. Front. Comput. Neurosci. (2015). http://dx.doi.org/10.3389/fncom.2015.0012

Pulsar Wind Nebulae with Bow Shocks: Non-thermal Radiation and Cosmic Ray Leptons

Pulsars with high spin-down power produce relativistic winds radiating a non-negligible fraction of this power over the whole electromagnetic range from radio to gamma-rays in the pulsar wind nebulae (PWNe). The rest of the power is dissipated in the interactions of the PWNe with the ambient interstellar medium (ISM). Some of the PWNe are moving relative to the ambient ISM with supersonic speeds producing bow shocks. In this case, the ultrarelativistic particles accelerated at the termination surface of the pulsar wind may undergo reacceleration in the converging flow system formed by the plasma outflowing from the wind termination shock and the plasma inflowing from the bow shock. The presence of magnetic perturbations in the flow, produced by instabilities induced by the accelerated particles themselves, is essential for the process to work. A generic outcome of this type of reacceleration is the creation of particle distributions with very hard spectra, such as are indeed required to explain the observed spectra of synchrotron radiation with photon indices Γ≲ 1.5. The presence of this hard spectral component is specific to PWNe with bow shocks (BSPWNe). The accelerated particles, mainly electrons and positrons, may end up containing a substantial fraction of the shock ram pressure. In addition, for typical ISM and pulsar parameters, the e+ released by these systems in the Galaxy are numerous enough to contribute a substantial fraction of the positrons detected as cosmic ray (CR) particles above few tens of GeV and up to several hundred GeV. The escape of ultrarelativistic particles from a BSPWN—and hence, its appearance in the far-UV and X-ray bands—is determined by the relative directions of the interstellar magnetic field, the velocity of the astrosphere and the pulsar rotation axis. In this respect we review the observed appearance and multiwavelength spectra of three different types of BSPWNe: PSR J0437-4715, the Guitar and Lighthouse nebulae, and Vela-like objects. We argue that high resolution imaging of such objects provides unique information both on pulsar winds and on the ISM. We discuss the interpretation of imaging observations in the context of the model outlined above and estimate the BSPWN contribution to the positron flux observed at the Earth

The spectral energy distribution of fermi bright blazars

We have conducted a detailed investigation of the broadband spectral properties of the γ-ray selected blazars of the Fermi LAT Bright AGN Sample (LBAS). By combining our accurately estimated Fermi γ-ray spectra with Swift, radio, infra-red, optical, and other hard X-ray/γ-ray data, collected within 3 months of the LBAS data taking period, we were able to assemble high-quality and quasi-simultaneous spectral energy distributions (SED) for 48 LBAS blazars. The SED of these γ-ray sources is similar to that of blazars discovered at other wavelengths, clearly showing, in the usual log ν-log ν Fν representation, the typical broadband spectral signatures normally attributed to a combination of low-energy synchrotron radiation followed by inverse Compton emission of one or more components. We have used these SED to characterize the peak intensity of both the low- and the high-energy components. The results have been used to derive empirical relationships that estimate the position of the two peaks from the broadband colors (i.e., the radio to optical, αro, and optical to X-ray, αox, spectral slopes) and from the γ-ray spectral index. Our data show that the synchrotron peak frequency (νSpeak) is positioned between 1012.5 and 1014.5 Hz in broad-lined flat spectrum radio quasars (FSRQs) and between 10 13 and 1017 Hz in featureless BL Lacertae objects. We find that the γ-ray spectral slope is strongly correlated with the synchrotron peak energy and with the X-ray spectral index, as expected at first order in synchrotron-inverse Compton scenarios. However, simple homogeneous, one-zone, synchrotron self-Compton (SSC) models cannot explain most of our SED, especially in the case of FSRQs and low energy peaked (LBL) BL Lacs. More complex models involving external Compton radiation or multiple SSC components are required to reproduce the overall SED and the observed spectral variability. While more than 50% of known radio bright high energy peaked (HBL) BL Lacs are detected in the LBAS sample, only less than 13% of known bright FSRQs and LBL BL Lacs are included. This suggests that the latter sources, as a class, may be much fainter γ-ray emitters than LBAS blazars, and could in fact radiate close to the expectations of simple SSC models. We categorized all our sources according to a new physical classification scheme based on the generally accepted paradigm for Active Galactic Nuclei and on the results of this SED study. Since the LAT detector is more sensitive to flat spectrum γ-ray sources, the correlation between νSpeak and γ-ray spectral index strongly favors the detection of high energy peaked blazars, thus explaining the Fermi overabundance of this type of sources compared to radio and EGRET samples. This selection effect is similar to that experienced in the soft X-ray band where HBL BL Lacs are the dominant type of blazars. © 2010 The American Astronomical Society

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

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Infectious and Whole Inactivated Simian Immunodeficiency Viruses Interact Similarly with Primate Dendritic Cells (DCs): Differential Intracellular Fate of Virions in Mature and Immature DCs

As potential targets for human immunodeficiency virus type 1 and simian immunodeficiency virus (HIV-1 and SIV), dendritic cells (DCs) likely play a significant role in the onset and spread of infection as well as in the induction of antiviral immunity. Using the SIV-macaque system to study the very early events in DC-virus interactions, we compared chemically inactivated SIV having conformationally and functionally intact envelope glycoproteins (2,2′-dithiodipyridine [AT-2] SIV) to infectious and heat-treated SIV. Both human and macaque DCs interact similarly with SIV without detectable effects on DC viability, phenotype, or endocytic function. As assessed by measuring cell-associated viral RNA, considerable amounts of virus are captured by the DCs and this is reduced when the virus is heat treated or derived from a strain that expresses low levels of envelope glycoprotein. Immunostaining for SIV proteins and electron microscopy indicated that few intact virus particles are retained at the periphery of the endocytically active, immature DCs. This contrasts with a perinuclear localization of numerous virions in large vesicular compartments deeper within mature DCs (in which macropinocytosis is down-regulated). Both immature and mature DCs are capable of clathrin-coated pit-mediated uptake of SIV, supporting the notion that the receptor-mediated uptake of virus can occur readily in mature DCs. While large numbers of whole viruses were preferentially found in mature DCs, both immature and mature DCs contained similar amounts of viral RNA, suggesting that different uptake/virus entry mechanisms are active in immature and mature DCs. These findings have significant implications for cell-to-cell transmission of HIV-1 and SIV and support the use of AT-2 SIV, an authentic but noninfectious form of virus, as a useful tool for studies of processing and presentation of AT-2 SIV antigens by DCs

Association of a variable number tandem repeat in the NLRP3 gene in women with susceptibility to RVVC

Vaginal infections with Candida spp. frequently occur in women of childbearing age. A small proportion of these women experience recurrent vulvovaginal candidosis (RVVC), which is characterized by at least three episodes of infection in one year. In addition to known risk factors such as antibiotics, diabetes, or pregnancy, host genetic variation and inflammatory pathways such as the IL-1/Th17 axis have been reported to play a substantial role in the pathogenesis of RVVC. In this study, we assessed a variable number tandem repeat (VNTR) polymorphism in the NLRP3 gene that encodes a component of the inflammasome, processing the proinflammatory cytokines IL-1beta and IL-18. A total of 270 RVVC patients and 583 healthy controls were analyzed, and increased diseases susceptibility was associated with the presence of the 12/9 genotype. Furthermore, functional studies demonstrate that IL-1beta production at the vaginal surface is higher in RVVC patients bearing the 12/9 genotype compared to controls, whereas IL-1Ra levels were decreased and IL-18 levels remained unchanged. These findings suggest that IL-1beta-mediated hyperinflammation conveyed by the NLRP3 gene plays a causal role in the pathogenesis of RVVC and may identify this pathway as a potential therapeutic target in the disease