141 research outputs found
Betti numbers for numerical semigroup rings
We survey results related to the magnitude of the Betti numbers of numerical
semigroup rings and of their tangent cones.Comment: 22 pages; v2: updated references. To appear in Multigraded Algebra
and Applications (V. Ene, E. Miller Eds.
Blocking TLR7- and TLR9-mediated IFN-α Production by Plasmacytoid Dendritic Cells Does Not Diminish Immune Activation in Early SIV Infection
Persistent production of type I interferon (IFN) by activated plasmacytoid dendritic cells (pDC) is a leading model to explain chronic immune activation in human immunodeficiency virus (HIV) infection but direct evidence for this is lacking. We used a dual antagonist of Toll-like receptor (TLR) 7 and TLR9 to selectively inhibit responses of pDC but not other mononuclear phagocytes to viral RNA prior to and for 8 weeks following pathogenic simian immunodeficiency virus (SIV) infection of rhesus macaques. We show that pDC are major but not exclusive producers of IFN-α that rapidly become unresponsive to virus stimulation following SIV infection, whereas myeloid DC gain the capacity to produce IFN-α, albeit at low levels. pDC mediate a marked but transient IFN-α response in lymph nodes during the acute phase that is blocked by administration of TLR7 and TLR9 antagonist without impacting pDC recruitment. TLR7 and TLR9 blockade did not impact virus load or the acute IFN-α response in plasma and had minimal effect on expression of IFN-stimulated genes in both blood and lymph node. TLR7 and TLR9 blockade did not prevent activation of memory CD4+ and CD8+ T cells in blood or lymph node but led to significant increases in proliferation of both subsets in blood following SIV infection. Our findings reveal that virus-mediated activation of pDC through TLR7 and TLR9 contributes to substantial but transient IFN-α production following pathogenic SIV infection. However, the data indicate that pDC activation and IFN-α production are unlikely to be major factors in driving immune activation in early infection. Based on these findings therapeutic strategies aimed at blocking pDC function and IFN-α production may not reduce HIV-associated immunopathology. © 2013 Kader et al
HIV/SIV Infection Primes Monocytes and Dendritic Cells for Apoptosis
Subversion or exacerbation of antigen-presenting cells (APC) death modulates host/pathogen equilibrium. We demonstrated during in vitro differentiation of monocyte-derived macrophages and monocyte-derived dendritic cells (DCs) that HIV sensitizes the cells to undergo apoptosis in response to TRAIL and FasL, respectively. In addition, we found that HIV-1 increased the levels of pro-apoptotic Bax and Bak molecules and decreased the levels of anti-apoptotic Mcl-1 and FLIP proteins. To assess the relevance of these observations in the context of an experimental model of HIV infection, we investigated the death of APC during pathogenic SIV-infection in rhesus macaques (RMs). We demonstrated increased apoptosis, during the acute phase, of both peripheral blood DCs and monocytes (CD14+) from SIV+RMs, associated with a dysregulation in the balance of pro- and anti-apoptotic molecules. Caspase-inhibitor and death receptors antagonists prevented apoptosis of APCs from SIV+RMs. Furthermore, increased levels of FasL in the sera of pathogenic SIV+RMs were detected, compared to non-pathogenic SIV infection of African green monkey. We suggest that inappropriate apoptosis of antigen-presenting cells may contribute to dysregulation of cellular immunity early in the process of HIV/SIV infection
TRAF6 and IRF7 Control HIV Replication in Macrophages
The innate immune system recognizes virus infection and evokes antiviral responses which include producing type I interferons (IFNs). The induction of IFN provides a crucial mechanism of antiviral defense by upregulating interferon-stimulated genes (ISGs) that restrict viral replication. ISGs inhibit the replication of many viruses by acting at different steps of their viral cycle. Specifically, IFN treatment prior to in vitro human immunodeficiency virus (HIV) infection stops or significantly delays HIV-1 production indicating that potent inhibitory factors are generated. We report that HIV-1 infection of primary human macrophages decreases tumor necrosis factor receptor-associated factor 6 (TRAF6) and virus-induced signaling adaptor (VISA) expression, which are both components of the IFN signaling pathway controlling viral replication. Knocking down the expression of TRAF6 in macrophages increased HIV-1 replication and augmented the expression of IRF7 but not IRF3. Suppressing VISA had no impact on viral replication. Overexpression of IRF7 resulted in enhanced viral replication while knocking down IRF7 expression in macrophages significantly reduced viral output. These findings are the first demonstration that TRAF6 can regulate HIV-1 production and furthermore that expression of IRF7 promotes HIV-1 replication
Innate immunity against HIV: a priority target for HIV prevention research
This review summarizes recent advances and current gaps in understanding of innate immunity to human immunodeficiency virus (HIV) infection, and identifies key scientific priorities to enable application of this knowledge to the development of novel prevention strategies (vaccines and microbicides). It builds on productive discussion and new data arising out of a workshop on innate immunity against HIV held at the European Commission in Brussels, together with recent observations from the literature
Gaia Focused Product Release: A catalogue of sources around quasars to search for strongly lensed quasars
Context. Strongly lensed quasars are fundamental sources for cosmology. The
Gaia space mission covers the entire sky with the unprecedented resolution of
" in the optical, making it an ideal instrument to search for
gravitational lenses down to the limiting magnitude of 21. Nevertheless, the
previous Gaia Data Releases are known to be incomplete for small angular
separations such as those expected for most lenses. Aims. We present the Data
Processing and Analysis Consortium GravLens pipeline, which was built to
analyse all Gaia detections around quasars and to cluster them into sources,
thus producing a catalogue of secondary sources around each quasar. We analysed
the resulting catalogue to produce scores that indicate source configurations
that are compatible with strongly lensed quasars. Methods. GravLens uses the
DBSCAN unsupervised clustering algorithm to detect sources around quasars. The
resulting catalogue of multiplets is then analysed with several methods to
identify potential gravitational lenses. We developed and applied an outlier
scoring method, a comparison between the average BP and RP spectra of the
components, and we also used an extremely randomised tree algorithm. These
methods produce scores to identify the most probable configurations and to
establish a list of lens candidates. Results. We analysed the environment of 3
760 032 quasars. A total of 4 760 920 sources, including the quasars, were
found within 6" of the quasar positions. This list is given in the Gaia
archive. In 87\% of cases, the quasar remains a single source, and in 501 385
cases neighbouring sources were detected. We propose a list of 381 lensed
candidates, of which we identified 49 as the most promising. Beyond these
candidates, the associate tables in this Focused Product Release allow the
entire community to explore the unique Gaia data for strong lensing studies
further.Comment: 35 pages, 60 figures, accepted for publication by Astronomy and
Astrophysic
Gaia Focused Product Release: Radial velocity time series of long-period variables
The third Gaia Data Release (DR3) provided photometric time series of more
than 2 million long-period variable (LPV) candidates. Anticipating the
publication of full radial-velocity (RV) in DR4, this Focused Product Release
(FPR) provides RV time series for a selection of LPVs with high-quality
observations. We describe the production and content of the Gaia catalog of LPV
RV time series, and the methods used to compute variability parameters
published in the Gaia FPR. Starting from the DR3 LPVs catalog, we applied
filters to construct a sample of sources with high-quality RV measurements. We
modeled their RV and photometric time series to derive their periods and
amplitudes, and further refined the sample by requiring compatibility between
the RV period and at least one of the , , or
photometric periods. The catalog includes RV time series and variability
parameters for 9\,614 sources in the magnitude range , including a flagged top-quality subsample of 6\,093 stars
whose RV periods are fully compatible with the values derived from the ,
, and photometric time series. The RV time series
contain a mean of 24 measurements per source taken unevenly over a duration of
about three years. We identify the great most sources (88%) as genuine LPVs,
with about half of them showing a pulsation period and the other half
displaying a long secondary period. The remaining 12% consists of candidate
ellipsoidal binaries. Quality checks against RVs available in the literature
show excellent agreement. We provide illustrative examples and cautionary
remarks. The publication of RV time series for almost 10\,000 LPVs constitutes,
by far, the largest such database available to date in the literature. The
availability of simultaneous photometric measurements gives a unique added
value to the Gaia catalog (abridged)Comment: 36 pages, 38 figure
Gaia Early Data Release 3 Acceleration of the Solar System from Gaia astrometry
Context. Gaia Early Data Release 3 (Gaia EDR3) provides accurate astrometry for about 1.6 million compact (QSO-like) extragalactic sources, 1.2 million of which have the best-quality five-parameter astrometric solutions. Aims. The proper motions of QSO-like sources are used to reveal a systematic pattern due to the acceleration of the solar systembarycentre with respect to the rest frame of the Universe. Apart from being an important scientific result by itself, the acceleration measured in this way is a good quality indicator of the Gaia astrometric solution. Methods. Theeffect of the acceleration was obtained as a part of the general expansion of the vector field of proper motions in vector spherical harmonics (VSH). Various versions of the VSH fit and various subsets of the sources were tried and compared to get the most consistent result and a realistic estimate of its uncertainty. Additional tests with the Gaia astrometric solution were used to get a better idea of the possible systematic errors in the estimate. Results. Our best estimate of the acceleration based on Gaia EDR3 is (2.32 +/- 0.16) x 10(-10) m s(-2) (or 7.33 +/- 0.51 km s(-1) Myr-1) towards alpha = 269.1 degrees +/- 5.4 degrees, delta = -31.6 degrees +/- 4.1 degrees, corresponding to a proper motion amplitude of 5.05 +/- 0.35 mu as yr(-1). This is in good agreement with the acceleration expected from current models of the Galactic gravitational potential. We expect that future Gaia data releases will provide estimates of the acceleration with uncertainties substantially below 0.1 mu as yr(-1).Peer reviewe
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