Infection by the human immunodeficiency virus (HIV) either upregulates or downregulates the expression of several cytokines and interferons (IFNs) that use the Janus kinase/signal transducer and ...activator of transcription (JAK/STAT) pathway for signal transduction. However, very little is known on the state of activation of the JAK/STAT pathway after HIV infection either in vivo or in vitro. In this regard, we report here that a constitutive activation of a C-terminal truncated STAT5 (STAT5▵) and of STAT1α occurs in the majority (∼75%) of individuals with progressive HIV disease. We have further demonstrated that, among peripheral blood mononuclear cells (PBMCs), STAT5▵ is activated preferentially in CD4+ T cells. In contrast to a published report, expression of STATs from PBMCs of infected individuals was comparable with that of seronegative donors. In addition, in vitro infection of mitogen-activated PBMCs with a panel of laboratory-adapted and primary HIV strains characterized by differential usage of chemokine coreceptors did not affect STAT protein levels. However, enhanced activation of STAT was observed after in vitro infection of resting PBMCs and nonadherent PBMCs by different viral strains. Thus, constitutive STAT activation in CD4+T lymphocytes represents a novel finding of interest also as a potential new marker of immunological reconstitution of HIV-infected individuals.
Linelike features in TeV γ rays constitute a "smoking gun" for TeV-scale particle dark matter and new physics. Probing the Galactic Center region with ground-based Cherenkov telescopes enables the ...search for TeV spectral features in immediate association with a dense dark matter reservoir at a sensitivity out of reach for satellite γ-ray detectors, and direct detection and collider experiments. We report on 223 hours of observations of the Galactic Center region with the MAGIC stereoscopic telescope system reaching γ-ray energies up to 100 TeV. We improved the sensitivity to spectral lines at high energies using large-zenith-angle observations and a novel background modeling method within a maximum-likelihood analysis in the energy domain. No linelike spectral feature is found in our analysis. Therefore, we constrain the cross section for dark matter annihilation into two photons to ⟨σv⟩≲5×10^{-28} cm^{3} s^{-1} at 1 TeV and ⟨σv⟩≲1×10^{-25} cm^{3} s^{-1} at 100 TeV, achieving the best limits to date for a dark matter mass above 20 TeV and a cuspy dark matter profile at the Galactic Center. Finally, we use the derived limits for both cuspy and cored dark matter profiles to constrain supersymmetric wino models.
MAGIC detection of GRB 201216C at z = 1.1 Acciari, V A; Agudo, I; Aniello, T ...
Monthly Notices of the Royal Astronomical Society,
01/2024, Letnik:
527, Številka:
3
Journal Article
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ABSTRACT
Gamma-ray bursts (GRBs) are explosive transient events occurring at cosmological distances, releasing a large amount of energy as electromagnetic radiation over several energy bands. We ...report the detection of the long GRB 201216C by the MAGIC telescopes. The source is located at z = 1.1 and thus it is the farthest one detected at very high energies. The emission above 70 GeV of GRB 201216C is modelled together with multiwavelength data within a synchrotron and synchrotron self-Compton (SSC) scenario. We find that SSC can explain the broad-band data well from the optical to the very-high-energy band. For the late-time radio data, a different component is needed to account for the observed emission. Differently from previous GRBs detected in the very-high-energy range, the model for GRB 201216C strongly favours a wind-like medium. The model parameters have values similar to those found in past studies of the afterglows of GRBs detected up to GeV energies.
Aims.
The BL Lac 1ES 2344+514 is known for temporary extreme properties characterised by a shift of the synchrotron spectral energy distribution (SED) peak energy
ν
synch, p
above 1 keV. While those ...extreme states have only been observed during high flux levels thus far, additional multi-year observing campaigns are required to achieve a coherent picture. Here, we report the longest investigation of the source from radio to very high energy (VHE) performed so far, focussing on a systematic characterisation of the intermittent extreme states.
Methods.
We organised a monitoring campaign covering a 3-year period from 2019 to 2021. More than ten instruments participated in the observations in order to cover the emission from radio to VHE. In particular, sensitive X-ray measurements by
XMM-Newton
,
NuSTAR
, and AstroSat took place simultaneously with multi-hour MAGIC observations, providing an unprecedented constraint of the two SED components for this blazar.
Results.
While our results confirm that 1ES 2344+514 typically exhibits
ν
synch, p
> 1 keV during elevated flux periods, we also find periods where the extreme state coincides with low flux activity. A strong spectral variability thus happens in the quiescent state, and is likely caused by an increase in the electron acceleration efficiency without a change in the electron injection luminosity. On the other hand, we also report a strong X-ray flare (among the brightest for 1ES 2344+514) without a significant shift of
ν
synch, p
. During this particular flare, the X-ray spectrum is among the softest of the campaign. It unveils complexity in the spectral evolution, where the common harder-when-brighter trend observed in BL Lacs is violated. By combining
Swift
-XRT and
Swift
-UVOT measurements during a low and hard X-ray state, we find an excess of the UV flux with respect to an extrapolation of the X-ray spectrum to lower energies. This UV excess implies that at least two regions significantly contribute to the infrared/optical/ultraviolet/X-ray emission. Using the simultaneous MAGIC,
XMM-Newton
,
NuSTAR
, and AstroSat observations, we argue that a region possibly associated with the 10 GHz radio core may explain such an excess. Finally, we investigate a VHE flare, showing an absence of simultaneous variability in the 0.3−2 keV band. Using time-dependent leptonic modelling, we show that this behaviour, in contradiction to single-zone scenarios, can instead be explained by a two-component model.
ABSTRACT
PG 1553 + 113 is one of the few blazars with a convincing quasi-periodic emission in the gamma-ray band. The source is also a very high energy (VHE; >100 GeV) gamma-ray emitter. To better ...understand its properties and identify the underlying physical processes driving its variability, the MAGIC Collaboration initiated a multiyear, multiwavelength monitoring campaign in 2015 involving the OVRO 40-m and Medicina radio telescopes, REM, KVA, and the MAGIC telescopes, Swift and Fermi satellites, and the WEBT network. The analysis presented in this paper uses data until 2017 and focuses on the characterization of the variability. The gamma-ray data show a (hint of a) periodic signal compatible with literature, but the X-ray and VHE gamma-ray data do not show statistical evidence for a periodic signal. In other bands, the data are compatible with the gamma-ray period, but with a relatively high p-value. The complex connection between the low- and high-energy emission and the non-monochromatic modulation and changes in flux suggests that a simple one-zone model is unable to explain all the variability. Instead, a model including a periodic component along with multiple emission zones is required.
Aims.
We have performed the first broadband study of Mrk 421 from radio to TeV gamma rays with simultaneous measurements of the X-ray polarization from IXPE.
Methods.
The data were collected as part ...of an extensive multiwavelength campaign carried out between May and June 2022 using MAGIC,
Fermi
-LAT,
NuSTAR
,
XMM-Newton
,
Swift
, and several optical and radio telescopes to complement IXPE data.
Results.
During the IXPE exposures, the measured 0.2–1 TeV flux was close to the quiescent state and ranged from 25% to 50% of the Crab Nebula without intra-night variability. Throughout the campaign, the very high-energy (VHE) and X-ray emission are positively correlated at a 4
σ
significance level. The IXPE measurements reveal an X-ray polarization degree that is a factor of 2–5 higher than in the optical/radio bands; that implies an energy-stratified jet in which the VHE photons are emitted co-spatially with the X-rays, in the vicinity of a shock front. The June 2022 observations exhibit a rotation of the X-ray polarization angle. Despite no simultaneous VHE coverage being available during a large fraction of the swing, the
Swift
-XRT monitoring reveals an X-ray flux increase with a clear spectral hardening. This suggests that flares in high synchrotron peaked blazars can be accompanied by a polarization angle rotation, as observed in some flat spectrum radio quasars. Finally, during the polarization angle rotation,
NuSTAR
data reveal two contiguous spectral hysteresis loops in opposite directions (clockwise and counterclockwise), implying important changes in the particle acceleration efficiency on approximately hour timescales.
We present a novel approach to the determination of the pointing of Imaging Atmospheric Cherenkov Telescopes (IACTs) using the trajectories of the stars in their camera’s field of view. The method ...starts with the reconstruction of the star positions from the Cherenkov camera data, taking into account the point spread function of the telescope, to achieve a satisfying reconstruction accuracy of the pointing position. A simultaneous fit of all reconstructed star trajectories is then performed with the orthogonal distance regression (ODR) method. ODR allows us to correctly include the star position uncertainties and use the time as an independent variable. Having the time as an independent variable in the fit makes it better suitable for various star trajectories. This method can be applied to any IACT and requires neither specific hardware nor interface or special data-taking mode. In this paper, we use the Large-Sized Telescope (LST) data to validate it as a useful tool to improve the determination of the pointing direction during regular data taking. The simulation studies show that the accuracy and precision of the method are comparable with the design requirements on the pointing accuracy of the LST (≤14″). With the typical LST event acquisition rate of 10 kHz, the method can achieve up to 50 Hz pointing monitoring rate, compared to ??(1) Hz achievable with standard techniques. The application of the method to the LST prototype (LST-1) commissioning data shows the stable pointing performance of the telescope.
IFN-gamma induces transcription of several IFN-stimulated genes (ISGs). Recently, the IFN-gamma-dependent Janus kinase (JAK)/STAT pathway has been shown to mediate the activation of some ISGs, by the ...sequential phosphorylation of two JAK kinases (JAK1 and JAK2) and of STAT1. Given that the JAK/STAT is the major, but not the only pathway linked to the IFN-gammaR, aim of our work was to investigate the signal-transduction pathway(s) by which IFN-gamma exerts its effects on acute replication of HIV in monocytic cells. To this end, we utilized clones previously derived from the U937 promonocytic cell line, differing for their efficient (plus clones) or inefficient (minus clones) abilities of supporting HIV replication. Unlike IFN-alpha, IFN-gamma did not inhibit HIV replication in plus clones, whereas virus production in minus cells was efficiently inhibited by both types of IFN. Plus clones generated a JAK/STAT signal-transduction pathway in response to IFN-alpha, but not IFN-gamma. In contrast, minus clones responded to either cytokines. The functional defect of plus clones in response to IFN-gamma was correlated to a selective defect of IFN-gammaR2, but not IFN-gammaR1, membrane expression. Surprisingly enough, IFN-gamma stimulation of plus clones induced IFN-stimulated gene factor 3 (ISGF3gamma). These results strongly support the hypothesis that the JAK/STAT pathway is responsible for the antiretroviral effect of IFN-gamma, and further provide evidence for a potential second pathway triggered by IFN-gamma in the absence of IFN-gammaR2 chain cell surface expression and involving ISGF3gamma.
Leader binding protein-1 (LBP-1)/late SV40 factor (LSF) and ying yang-1 (YY1) transcription factors are involved in the regulation of HIV expression. In particular, YY1 and LBP-1 have been shown to ...cooperate in repressing HIV-1-long terminal repeat reporter gene expression by in vitro cotransfection experiments. However, no information is available on the levels of expression and activation of these transcription factors in PBMC of HIV-infected individuals. Therefore, we have evaluated the expression and DNA binding activity of YY1 and LBP-1 (LSF) in PBMC of HIV-infected individuals before, during, and after administration of IL-2 in association with antiretroviral therapy (ART), a regimen under consideration for broad clinical use in this disease based on its ability to stably raise the absolute number of circulating CD4+ T lymphocytes. Both YY1- and LBP-1 (LSF)-DNA binding were profoundly down-modulated during administration of IL-2/ART, and a proteolytic activity probably responsible for the reduced expression of the two cellular transcription factors was found activated in PBMC of individuals receiving the immunotherapeutic regimen. This study is the first evidence of modulation of cellular transcription factors following IL-2/ART administration and provides a potential correlate of the transient raises in plasma viremia early reported in patients receiving IL-2 in the absence of ART, thus underscoring the importance of always administering this cytokine to HIV-infected individuals together with potent antiretrovirals.
