Showing papers by "University of Rijeka published in 2012"

One or more bound planets per Milky Way star from microlensing observations

Abstract: Most known extrasolar planets (exoplanets) have been discovered using the radial velocity or transit methods. Both are biased towards planets that are relatively close to their parent stars, and studies find that around 17–30% of solar-like stars host a planet. Gravitational microlensing on the other hand, probes planets that are further away from their stars. Recently, a population of planets that are unbound or very far from their stars was discovered by microlensing. These planets are at least as numerous as the stars in the Milky Way. Here we report a statistical analysis of microlensing data (gathered in 2002–07) that reveals the fraction of bound planets 0.5–10 au (Sun–Earth distance) from their stars. We find that 17^(+16)_(-9)% of stars host Jupiter-mass planets (0.3–10 M_J, where M_J = 318 M_⊕ plus and M_⊕ plus is Earth’s mass). Cool Neptunes (10–30 M_⊕ plus) and super-Earths (5–10 M_⊕ plus) are even more common: their respective abundances per star are 52^(+22)_(-29)% and 62^(+35)_(-73)% . We conclude that stars are orbited by planets as a rule, rather than the exception.

The 2010 very high energy gamma-ray flare and 10 years of multi-wavelength observations of M 87

Abstract: The giant radio galaxy M 87 with its proximity (16 Mpc), famous jet, and very massive black hole ((3-6) x 10(9) M-circle dot) provides a unique opportunity to investigate the origin of very high energy (VHE; E > 100 GeV) gamma-ray emission generated in relativistic outflows and the surroundings of supermassive black holes. M 87 has been established as a VHE gamma-ray emitter since 2006. The VHE gamma-ray emission displays strong variability on timescales as short as a day. In this paper, results from a joint VHE monitoring campaign on M 87 by the MAGIC and VERITAS instruments in 2010 are reported. During the campaign, a flare at VHE was detected triggering further observations at VHE (H.E.S.S.), X-rays (Chandra), and radio (43 GHz Very Long Baseline Array, VLBA). The excellent sampling of the VHE gamma-ray light curve enables one to derive a precise temporal characterization of the flare: the single, isolated flare is well described by a two-sided exponential function with significantly different flux rise and decay times of tau(rise)(d) = (1.69 +/- 0.30) days and tau(decay)(d) = (0.611 +/- 0.080) days, respectively. While the overall variability pattern of the 2010 flare appears somewhat different from that of previous VHE flares in 2005 and 2008, they share very similar timescales (similar to day), peak fluxes (Phi(>0.35 TeV) similar or equal to (1-3) x 10(-11) photons cm(-2) s(-1)), and VHE spectra. VLBA radio observations of 43 GHz of the inner jet regions indicate no enhanced flux in 2010 in contrast to observations in 2008, where an increase of the radio flux of the innermost core regions coincided with a VHE flare. On the other hand, Chandra X-ray observations taken similar to 3 days after the peak of the VHE gamma-ray emission reveal an enhanced flux from the core (flux increased by factor similar to 2; variability timescale <2 days). The long-term (2001-2010) multi-wavelength (MWL) light curve of M 87, spanning from radio to VHE and including data from Hubble Space Telescope, Liverpool Telescope, Very Large Array, and European VLBI Network, is used to further investigate the origin of the VHE gamma-ray emission. No unique, common MWL signature of the three VHE flares has been identified. In the outer kiloparsec jet region, in particular in HST-1, no enhanced MWL activity was detected in 2008 and 2010, disfavoring it as the origin of the VHE flares during these years. Shortly after two of the three flares (2008 and 2010), the X-ray core was observed to be at a higher flux level than its characteristic range (determined from more than 60 monitoring observations: 2002-2009). In 2005, the strong flux dominance of HST-1 could have suppressed the detection of such a feature. Published models for VHE gamma-ray emission from M 87 are reviewed in the light of the new data.

Degradation of cellular mir-27 by a novel, highly abundant viral transcript is important for efficient virus replication in vivo.

Abstract: Cytomegaloviruses express large amounts of viral miRNAs during lytic infection, yet, they only modestly alter the cellular miRNA profile. The most prominent alteration upon lytic murine cytomegalovirus (MCMV) infection is the rapid degradation of the cellular miR-27a and miR-27b. Here, we report that this regulation is mediated by the ∼1.7 kb spliced and highly abundant MCMV m169 transcript. Specificity to miR-27a/b is mediated by a single, apparently optimized, miRNA binding site located in its 3'-UTR. This site is easily and efficiently retargeted to other cellular and viral miRNAs by target site replacement. Expression of the 3'-UTR of m169 by an adenoviral vector was sufficient to mediate its function, indicating that no other viral factors are essential in this process. Degradation of miR-27a/b was found to be accompanied by 3'-tailing and -trimming. Despite its dramatic effect on miRNA stability, we found this interaction to be mutual, indicating potential regulation of m169 by miR-27a/b. Most interestingly, three mutant viruses no longer able to target miR-27a/b, either due to miRNA target site disruption or target site replacement, showed significant attenuation in multiple organs as early as 4 days post infection, indicating that degradation of miR-27a/b is important for efficient MCMV replication in vivo.

Mutual protection of ribosomal proteins L5 and L11 from degradation is essential for p53 activation upon ribosomal biogenesis stress

Abstract: Impairment of ribosomal biogenesis can activate the p53 protein independently of DNA damage. The ability of ribosomal proteins L5, L11, L23, L26, or S7 to bind Mdm2 and inhibit its ubiquitin ligase activity has been suggested as a critical step in p53 activation under these conditions. Here, we report that L5 and L11 are particularly important for this response. Whereas several other newly synthesized ribosomal proteins are degraded by proteasomes upon inhibition of Pol I activity by actinomycin D, L5 and L11 accumulate in the ribosome-free fraction where they bind to Mdm2. This selective accumulation of free L5 and L11 is due to their mutual protection from proteasomal degradation. Furthermore, the endogenous, newly synthesized L5 and L11 continue to be imported into nucleoli even after nucleolar disruption and colocalize with Mdm2, p53, and promyelocytic leukemia protein. This suggests that the disrupted nucleoli may provide a platform for L5- and L11-dependent p53 activation, implying a role for the nucleolus in p53 activation by ribosomal biogenesis stress. These findings may have important implications with respect to understanding the pathogenesis of diseases caused by impaired ribosome biogenesis.

Disordered IL-33/ST2 activation in decidualizing stromal cells prolongs uterine receptivity in women with recurrent pregnancy loss.

Abstract: Decidualization renders the endometrium transiently receptive to an implanting blastocyst although the underlying mechanisms remain incompletely understood. Here we show that human endometrial stromal cells (HESCs) rapidly release IL-33, a key regulator of innate immune responses, upon decidualization. In parallel, differentiating HESCs upregulate the IL-33 transmembrane receptor ST2L and other pro-inflammatory mediators before mounting a profound anti-inflammatory response that includes downregulation of ST2L and increased expression of the soluble decoy receptor sST2. We demonstrate that HESCs secrete factors permissive of embryo implantation in mice only during the pro-inflammatory phase of the decidual process. IL-33 knockdown in undifferentiated HESCs was sufficient to abrogate this pro-inflammatory decidual response. Further, sequential activation of the IL-33/ST2L/sST2 axis was disordered in decidualizing HESCs from women with recurrent pregnancy loss. Signals from these cultures prolonged the implantation window but also caused subsequent pregnancy failure in mice. Thus, Il-33/ST2 activation in HESCS drives an autoinflammatory response that controls the temporal expression of receptivity genes. Failure to constrain this response predisposes to miscarriage by allowing out-of-phase implantation in an unsupportive uterine environment.

Dynamic autoinoculation and the microbial ecology of a deep water hydrocarbon irruption

Abstract: The irruption of gas and oil into the Gulf of Mexico during the Deepwater Horizon event fed a deep sea bacterial bloom that consumed hydrocarbons in the affected waters, formed a regional oxygen anomaly, and altered the microbiology of the region. In this work, we develop a coupled physical–metabolic model to assess the impact of mixing processes on these deep ocean bacterial communities and their capacity for hydrocarbon and oxygen use. We find that observed biodegradation patterns are well-described by exponential growth of bacteria from seed populations present at low abundance and that current oscillation and mixing processes played a critical role in distributing hydrocarbons and associated bacterial blooms within the northeast Gulf of Mexico. Mixing processes also accelerated hydrocarbon degradation through an autoinoculation effect, where water masses, in which the hydrocarbon irruption had caused blooms, later returned to the spill site with hydrocarbon-degrading bacteria persisting at elevated abundance. Interestingly, although the initial irruption of hydrocarbons fed successive blooms of different bacterial types, subsequent irruptions promoted consistency in the structure of the bacterial community. These results highlight an impact of mixing and circulation processes on biodegradation activity of bacteria during the Deepwater Horizon event and suggest an important role for mixing processes in the microbial ecology of deep ocean environments.

The NK Cell Response to Mouse Cytomegalovirus Infection Affects the Level and Kinetics of the Early CD8+ T-Cell Response

Abstract: Natural killer (NK) cells and CD8+ T cells play a prominent role in the clearance of mouse cytomegalovirus (MCMV) infection. The role of NK cells in modulating the CD8+ T-cell response to MCMV infection is still the subject of intensive research. For analyzing the impact of NK cells on mounting of a CD8+ T-cell response and the contribution of these cells to virus control during the first days postinfection (p.i.), we used C57BL/6 mice in which NK cells are specifically activated through the Ly49H receptor engaged by the MCMV-encoded ligand m157. Our results indicate that the requirement for CD8+ T cells in early MCMV control inversely correlates with the engagement of Ly49H. While depletion of CD8+ T cells has only a minor effect on the early control of wild-type MCMV, CD8+ T cells are essential in the control of Δm157 virus. The frequencies of virus epitope-specific CD8+ T cells and their activation status were higher in mice infected with Δm157 virus. In addition, these mice showed elevated levels of alpha interferon (IFN-α) and several other proinflammatory cytokines as early as 1.5 days p.i. Although the numbers of conventional dendritic cells (cDCs) were reduced later during infection, particularly in Δm157-infected mice, they were not significantly affected at the peak of the cytokine response. Altogether, we concluded that increased antigen load, preservation of early cDCs' function, and higher levels of innate cytokines collectively account for an enhanced CD8+ T-cell response in C57BL/6 mice infected with a virus unable to activate NK cells via the Ly49H–m157 interaction.

Differential hepatoprotective mechanisms of rutin and quercetin in CCl(4)-intoxicated BALB/cN mice.

Abstract: To investigate the mechanisms underlying the protective effects of quercetin-rutinoside (rutin) and its aglycone quercetin against CCl4-induced liver damage in mice. BALB/cN mice were intraperitoneally administered rutin (10, 50, and 150 mg/kg) or quercetin (50 mg/kg) once daily for 5 consecutive days, followed by the intraperitoneal injection of CCl4 in olive oil (2 mL/kg, 10% v/v). The animals were sacrificed 24 h later. Blood was collected for measuring the activities of ALT and AST, and the liver was excised for assessing Cu/Zn superoxide dismutase (SOD) activity, GSH and protein concentrations and also for immunoblotting. Portions of the livers were used for histology and immunohistochemistry. Pretreatment with rutin and, to a lesser extent, with quercetin significantly reduced the activity of plasma transaminases and improved the histological signs of acute liver damage in CCl4-intoxicated mice. Quercetin prevented the decrease in Cu/Zn SOD activity in CCl4-intoxicated mice more potently than rutin. However, it was less effective in the suppression of nitrotyrosine formation. Quercetin and, to a lesser extent, rutin attenuated the inflammation in the liver by down-regulating the CCl4-induced activation of nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α) and cyclooxygenase (COX-2). The expression of inducible nitric oxide synthase (iNOS) was more potently suppressed by rutin than by quercetin. Treatment with both flavonoids significantly increased NF-E2-related factor 2 (Nrf2) and heme oxygenase (HO-1) expression in injured livers, although quercetin was less effective than rutin at an equivalent dose. Quercetin more potently suppressed the expression of transforming growth factor-β1 (TGF-β1) than rutin. Rutin exerts stronger protection against nitrosative stress and hepatocellular damage but has weaker antioxidant and anti-inflammatory activities and antifibrotic potential than quercetin, which may be attributed to the presence of a rutinoside moiety in position 3 of the C ring.

Detection of very high energy gamma-ray emission from NGC 1275 by the MAGIC telescopes

Abstract: We report on the detection of very-high energy (VHE, E > 100 GeV) -ray emission from NGC 1275, the central radio galaxy of the Perseus cluster of galaxies. The source has been detected by the MAGIC telescopes with a statistical significance of 6 .6 � above 100 GeV in 46 hr of stereo observations carried out between August 2010 and February 2011. The measured differential energy spectrum between 70 GeV and 500 GeV can be described by a power law with a steep spectral index of = −4.1± 0.7stat± 0.3syst, and the average flux above 100 GeV is F = (1.3± 0.2stat± 0.3syst)× 10 −11 cm −2 s −1 . These results, combined with the power-law spectrum measured in the first two years of observations by the Fermi‐LAT above 100 MeV, with a spectral index of ≃ −2.1, strongly suggest the presence of a break or cut-off around tens of GeV in the NGC 1275 spectrum. The light curve of the source above 100 GeV does not show hints of variability on a month time scale. Finally, we report on the nondetection in the present data of the radio galaxy IC 310, previously discovered by the Fermi‐LAT and MAGIC. The derived flux upper limit F U.L. (> 300 GeV) = 1.2× 10 −12 cm −2 s −1 is a factor∼ 3 lower than the mean flux measured by MAGIC between October 2009 and February 2010, thus confirming the year time-scale variabil ity of the source at VHE.

Changes in Cross-Correlations as an Indicator for Systemic Risk

Abstract: The 2008–2012 global financial crisis began with the global recession in December 2007 and exacerbated in September 2008, during which the U.S. stock markets lost 20% of value from its October 11 2007 peak. Various studies reported that financial crisis are associated with increase in both cross-correlations among stocks and stock indices and the level of systemic risk. In this paper, we study 10 different Dow Jones economic sector indexes, and applying principle component analysis (PCA) we demonstrate that the rate of increase in principle components with short 12-month time windows can be effectively used as an indicator of systemic risk—the larger the change of PC1, the higher the increase of systemic risk. Clearly, the higher the level of systemic risk, the more likely a financial crisis would occur in the near future.

Role of interleukin-1 inhibitors in osteoarthritis: an evidence-based review.

Abstract: Osteoarthritis (OA), the most common chronic musculoskeletal disease, represents a leading cause of disability in the elderly population worldwide. At present, there is no aetiological treatment for OA patients. Also, current therapeutic regimens for OA are only partially effective, and that is the main reason for most physicians’ complaints. Therefore, one of the biggest challenges in the future will be to find the most appropriate therapy or therapies for OA. Currently, there are three basic modalities of treatment: nonpharmacological, pharmacological and surgical. Regarding pharmacological treatment, numerous molecular pathways involved in the pathophysiology of OA have been investigated as potential therapeutic targets. In preclinical and clinical trials, many compounds and agents have been tested, and some of them have already shown positive effects on the progression of knee and/or hip OA. One such possible pharmacological treatment of OA is anticytokine therapy. Interleukin-1 (IL-1), as a main inflammatory and catabolic cytokine in the pathophysiology of OA, represents one of the possible treatment targets. For specific inhibition of IL-1 production or activity, various treatment strategies could be used. These include the inhibition or modification of IL-1 action through the application of IL-1 receptor antagonist proteins, soluble IL-1 receptors, monoclonal antibodies against IL-1 or against IL-1 receptor I, blocking the formation of active IL-1β, blocking the IL-1 cellular signalling pathways, or using gene therapy. All the abovementioned treatment strategies for specific inhibition of IL-1 production or activity have been investigated in numerous preclinical and clinical studies. Some of these investigations led to the discovery of new potential drugs for the treatment of OA. However, the results of treatment with these drugs were not entirely satisfactory, and further research is required to achieve the desired goals of therapy.

Morphological and spectral properties of the W51 region measured with the MAGIC telescopes

Abstract: The W51 complex hosts the supernova remnant W51C which is known to interact with the molecular clouds in the star forming region W51B. In addition, a possible pulsar wind nebula CXO J192318.5+140305 was found likely associated with the supernova remnant. Gamma-ray emission from this region was discovered by Fermi/LAT (between 0.2 and 50 GeV) and H. E. S. S. (>1 TeV). The spatial distribution of the events could not be used to pinpoint the location of the emission among the pulsar wind nebula, the supernova remnant shell and/or the molecular cloud. However, the modeling of the spectral energy distribution presented by the Fermi/LAT collaboration suggests a hadronic emission mechanism. The possibility that the gamma-ray emission from such an object is of hadronic origin can contribute to solvingthe long-standing problem of the contribution to galactic cosmic rays by supernova remnants. Aims. Our aim is to determine the morphology of the very-high-energy gamma-ray emission of W51 and measure its spectral properties. Methods. We performed observations of the W51 complex with the MAGIC telescopes for more than 50 h. The energy range accessible with MAGIC extends from 50 GeV to several TeV, allowing for the first spectral measurement at these energies. In addition, the good angular resolution in the medium (few hundred GeV) to high (above 1 TeV) energies allow us to perform morphological studies. We look for underlying structures by means of detailed morphological studies. Multi-wavelength data from this source have been sampled to model the emission with both leptonic and hadronic processes. Results. We detect an extended emission of very-high-energy gamma rays, with a significance of 11 standard deviations. We extend the spectrum from the highest Fermi/LAT energies to similar to 5 TeV and find that it follows a single power law with an index of 2.58 +/- 0.07(stat) +/- 0.22(syst). The main part of the emission coincides with the shocked cloud region, while we find a feature extending towards the pulsar wind nebula. The possible contribution of the pulsar wind nebula, assuming a point-like source, shows no dependence on energy and it is about 20% of the overall emission. The broad band spectral energy distribution can be explained with a hadronic model that implies proton acceleration above 100 TeV. This result, together with the morphology of the source, tentatively suggests that we observe ongoing acceleration of ions in the interaction zone between supernova remnant and cloud.

Phase-resolved energy spectra of the Crab Pulsar in the range of 50-400 GeV measured with the MAGIC Telescopes

Abstract: We use 73 h of stereoscopic data taken with the MAGIC telescopes to investigate the very high-energy (VHE) gamma-ray emission of the Crab pulsar. Our data show a highly significant pulsed signal in the energy range from 50 to 400 GeV in both the main pulse (P1) and the interpulse (P2) phase regions. We provide the widest spectra to date of the VHE components of both peaks, and these spectra extend to the energy range of satellite-borne observatories. The good resolution and background rejection of the stereoscopic MAGIC system allows us to cross-check the correctness of each spectral point of the pulsar by comparison with the corresponding (strong and well-known) Crab nebula flux. The spectra of both P1 and P2 are compatible with power laws with photon indices of 4.0 ± 0.8 (P1) and 3.42 ± 0.26 (P2), respectively, and the ratio P1/P2 between the photon counts of the two pulses is 0.54 ± 0.12. The VHE emission can be understood as an additional component produced by the inverse Compton scattering of secondary and tertiary e± pairs on IR-UV photons. © 2012 ESO.

Modeling damage in concrete caused by corrosion of reinforcement: coupled 3D FE model

Abstract: Reinforced concrete structures, which are exposed to aggressive environmental conditions, such as structures close to the sea or highway bridges and garages exposed to de-icing salts, often exhibit damage due to corrosion. Damage is usually manifested in the form of cracking and spalling of concrete cover caused by expansion of corrosion products around reinforcement. The reparation of corroded structure is related with relatively high direct and indirect costs. Therefore, it is of great importance to have a model, which is able to realistically predict influence of corrosion on the safety and durability of reinforced concrete structures. In the present contribution a 3D chemo-hygro-thermo-mechanical model for concrete is presented. In the model the interaction between non-mechanical influences (distribution of temperature, humidity, oxygen, chloride and rust) and mechanical properties of concrete (damage), is accounted for. The mechanical part of the model is based on the microplane model. It has recently been shown that the model is able to realistically describe the processes before and after depassivation of reinforcement and that it correctly accounts for the interaction between mechanical (damage) and non-mechanical processes in concrete. In the present paper application of the model is illustrated on two numerical examples. The first demonstrates the influence of expansion of corrosion products on damage of the beam specimen in cases with and without accounting for the transport of rust through cracks. It is shown that the transport of corrosion products through cracks can significantly influence the corrosion induced damage. In the second example the numerically predicted crack patterns due to corrosion of reinforcement in a beam are compared with experimental results. The influence of the anode–cathode regions on the corrosion induced damage is investigated. The comparison between numerical results and experimental evidence shows that the model is able to realistically predict experimentally observed crack pattern and that the position of anode and cathode strongly influences the crack pattern and corrosion rate.

Mrk 421 active state in 2008: the MAGIC view, simultaneous multi-wavelength observations and SSC model constrained

Abstract: The blazar Markarian 421 is one of the brightest TeV gamma-ray sources of the northern sky. From December 2007 until June 2008 it was intensively observed in the very high energy (VHE, E > 100 GeV) band by the single-dish Major Atmospheric Gamma-ray Imaging Cherenkov telescope (MAGIC-I). Aims. We aimed to measure the physical parameters of the emitting region of the blazar jet during active states. Methods. We performed a dense monitoring of the source in VHE with MAGIC-I, and also collected complementary data in soft X-rays and optical-UV bands; then, we modeled the spectral energy distributions (SED) derived from simultaneous multi-wavelength data within the synchrotron self-Compton (SSC) framework. Results. The source showed intense and prolonged.-ray activity during the whole period, with integral fluxes (E > 200 GeV) seldom below the level of the Crab Nebula, and up to 3.6 times this value. Eight datasets of simultaneous optical-UV (KVA, Swift/UVOT), soft X-ray (Swift/XRT) and MAGIC-I VHE data were obtained during different outburst phases. The data constrain the physical parameters of the jet, once the spectral energy distributions obtained are interpreted within the framework of a single-zone SSC leptonic model. Conclusions. The main outcome of the study is that within the homogeneous model high Doppler factors (40 <= delta <= 80) are needed to reproduce the observed SED; but this model cannot explain the observed short time-scale variability, while it can be argued that inhomogeneous models could allow for less extreme Doppler factors, more intense magnetic fields and shorter electron cooling times compatible with hour or sub-hour scale variability.

Morphological and spectral properties of the W51 region measured with the MAGIC telescopes

Abstract: The W51 complex hosts the supernova remnant W51C which is known to interact with the molecular clouds in the star forming region W51B. In addition, a possible pulsar wind nebula CXO J192318.5+140305 was found likely associated with the supernova remnant. Gamma-ray emission from this region was discovered by Fermi/LAT (between 0.2 and 50 GeV) and H.E.S.S. (>1 TeV). The spatial distribution of the events could not be used to pinpoint the location of the emission among the pulsar wind nebula, the supernova remnant shell and/or the molecular cloud. However, the modeling of the spectral energy distribution presented by the Fermi/LAT collaboration suggests a hadronic emission mechanism. We performed observations of the W51 complex with the MAGIC telescopes for more than 50 hours. The good angular resolution in the medium (few hundred GeV) to high (above 1 TeV) energies allow us to perform morphological studies. We detect an extended emission of very-high-energy gamma rays, with a significance of 11 standard deviations. We extend the spectrum from the highest Fermi/LAT energies to \sim 5 TeV and find that it follows a single power law with an index of 2.58 \pm 0.07stat \pm 0.22syst . The main part of the emission coincides with the shocked cloud region, while we find a feature extending towards the pulsar wind nebula. The possible contribution of the pulsar wind nebula, assuming a point-like source, shows no dependence on energy and it is about 20% of the overall emission. The broad band spectral energy distribution can be explained with a hadronic model that implies proton acceleration above 100 TeV. This result, together with the morphology of the source, tentatively suggests that we observe ongoing acceleration of ions in the interaction zone between supernova remnant and cloud. These results shed light on the long-standing problem of the origin of galactic cosmic rays.

IL-10 suppression of NK/DC crosstalk leads to poor priming of MCMV-specific CD4 T cells and prolonged MCMV persistence

Abstract: IL-10 is an anti-inflammatory cytokine that regulates the extent of host immunity to infection by exerting suppressive effects on different cell types. Herpes viruses induce IL-10 to modulate the virus-host balance towards their own benefit, resulting in prolonged virus persistence. To define the cellular and molecular players involved in IL-10 modulation of herpes virus-specific immunity, we studied mouse cytomegalovirus (MCMV) infection. Here we demonstrate that IL-10 specifically curtails the MCMV-specific CD4 T cell response by suppressing the bidirectional crosstalk between NK cells and myeloid dendritic cells (DCs). In absence of IL-10, NK cells licensed DCs to effectively prime MCMV-specific CD4 T cells and we defined the pro-inflammatory cytokines IL-12, IFN-γ and TNF-α as well as NK cell activating receptors NKG2D and NCR-1 to regulate this bidirectional NK/DC interplay. Consequently, markedly enhanced priming of MCMV-specific CD4 T cells in Il10−/− mice led to faster control of lytic viral replication, but this came at the expense of TNF-α mediated immunopathology. Taken together, our data show that early induction of IL-10 during MCMV infection critically regulates the strength of the innate-adaptive immune cell crosstalk, thereby impacting beneficially on the ensuing virus-host balance for both the virus and the host.

Discovery of VHE gamma-rays from the blazar 1ES 1215+303 with the MAGIC telescopes and simultaneous multi-wavelength observations

Abstract: Context. We present the discovery of very high energy (VHE, E > 100 GeV) gamma-ray emission from the BL Lac object 1ES 1215+303 by the MAGIC telescopes and simultaneous multi-wavelength data in a broad energy range from radio to gamma-rays. Aims. We study the VHE gamma-ray emission from 1ES 1215+303 and its relation to the emissions in other wavelengths. Methods. Triggered by an optical outburst, MAGIC observed the source in 2011 January-February for 20.3 h. The target was monitored in the optical R-band by the KVA telescope that also performed optical polarization measurements. We triggered target of opportunity observations with the Swift satellite and obtained simultaneous and quasi-simultaneous data from the Fermi Large Area Telescope and from the Metsahovi radio telescope. We also present the analysis of older MAGIC data taken in 2010. Results. The MAGIC observations of 1ES 1215+303 carried out in 2011 January-February resulted in the first detection of the source at VHE with a statistical significance of 9.4 sigma. Simultaneously, the source was observed in a high optical and X-ray state. In 2010 the source was observed in a lower state in optical, X-ray, and VHE, while the GeV gamma-ray flux and the radio flux were comparable in 2010 and 2011. The spectral energy distribution obtained with the 2011 data can be modeled with a simple one zone SSC model, but it requires extreme values for the Doppler factor or the electron energy distribution.

Mouse Hobit is a homolog of the transcriptional repressor Blimp-1 that regulates NKT cell effector differentiation

Abstract: The transcriptional repressor Blimp-1 mediates the terminal differentiation of many cell types, including T cells Here we identified Hobit (Znf683) as a previously unrecognized homolog of Blimp-1 that was specifically expressed in mouse natural killer T cells (NKT cells) Through studies of Hobit-deficient mice, we found that Hobit was essential for the formation of mature thymic NKT cells In the periphery, Hobit repressed the accumulation of interferon-γ (IFN-γ)-producing NK11(lo) NKT cells at steady state After antigenic stimulation, Hobit repressed IFN-γ expression, whereas after innate stimulation, Hobit induced granzyme B expression Thus, reminiscent of the function of Blimp-1 in other lymphocytes, Hobit controlled the maintenance of quiescent, fully differentiated NKT cells and regulated their immediate effector functions

NKG2D signaling on CD8⁺ T cells represses T-bet and rescues CD4-unhelped CD8⁺ T cell memory recall but not effector responses

Abstract: CD4-unhelped CD8(+) T cells are functionally defective T cells primed in the absence of CD4(+) T cell help. Given the co-stimulatory role of natural-killer group 2, member D protein (NKG2D) on CD8(+) T cells, we investigated its ability to rescue these immunologically impotent cells. We demonstrate that augmented co-stimulation through NKG2D during priming paradoxically rescues memory, but not effector, CD8(+) T cell responses. NKG2D-mediated rescue is characterized by reversal of elevated transcription factor T-box expressed in T cells (T-bet) expression and recovery of interleukin-2 and interferon-γ production and cytolytic responses. Rescue is abrogated in CD8(+) T cells lacking NKG2D. Augmented co-stimulation through NKG2D confers a high rate of survival to mice lacking CD4(+) T cells in a CD4-dependent influenza model and rescues HIV-specific CD8(+) T cell responses from CD4-deficient HIV-positive donors. These findings demonstrate that augmented co-stimulation through NKG2D is effective in rescuing CD4-unhelped CD8(+) T cells from their pathophysiological fate and may provide therapeutic benefits.

Optomechanical sideband cooling of a thin membrane within a cavity

Abstract: We present an experimental study of dynamical back-action cooling of the fundamental vibrational mode of a thin semitransparent membrane placed within a high-finesse optical cavity We study how the radiation?pressure interaction modifies the mechanical response of the vibrational mode, and the experimental results are in agreement with a Langevin equation description of the coupled dynamics The experiments are carried out in the resolved sideband regime, and we have observed cooling by a factor of ?350 We have also observed the mechanical frequency shift associated with the quadratic term in the expansion of the cavity mode frequency versus the effective membrane position, which is typically negligible in other cavity optomechanical devices

Discovery of VHE gamma-rays from the blazar 1ES 1215+303 with the MAGIC Telescopes and simultaneous multi-wavelength observations

Abstract: Context. We present the discovery of very high energy (VHE, E > 100GeV) gamma-ray emission from the BL Lac object 1ES 1215+303 by the MAGIC telescopes and simultaneous multi-wavelength data in a broad energy range from radio to gamma-rays. Aims. We study the VHE gamma-ray emission from 1ES 1215+303 and its relation to the emissions in other wavelengths. Methods. Triggered by an optical outburst, MAGIC observed the source in January-February 2011 for 20.3 hrs. The target was monitored in the optical R-band by the KVA telescope that also performed optical polarization measurements. We triggered target of opportunity observations with the Swift satellite and obtained simultaneous and quasi-simultaneous data from the Fermi Large Area Telescope and from the Metsahovi radio telescope. We also present the analysis of older MAGIC data taken in 2010. Results. The MAGIC observations of 1ES 1215+303 carried out in January-February 2011 resulted in the first detection of the source at VHE with a statistical significance of 9.4 sigma. Simultaneously, the source was observed in a high optical and X-ray state. In 2010 the source was observed in a lower state in optical, X-ray, and VHE, while the GeV gamma-ray flux and the radio flux were comparable in 2010 and 2011. The spectral energy distribution obtained with the 2011 data can be modeled with a simple one zone SSC model, but it requires extreme values for the Doppler factor or the electron energy distribution.

Elucidating the mechanisms of influenza virus recognition by Ncr1.

Abstract: Natural killer (NK) cells are innate cytotoxic lymphocytes that specialize in the defense against viral infection and oncogenic transformation. Their action is tightly regulated by signals derived from inhibitory and activating receptors; the later include proteins such as the Natural Cytotoxicity Receptors (NCRs: NKp46, NKp44 and NKp30). Among the NCRs, NKp46 is the only receptor that has a mouse orthologue named Ncr1. NKp46/Ncr1 is also a unique marker expressed on NK and on Lymphoid tissue inducer (LTI) cells and it was implicated in the control of various viral infections, cancer and diabetes. We have previously shown that human NKp46 recognizes viral hemagglutinin (HA) in a sialic acid-dependent manner and that the O-glycosylation is essential for the NKp46 binding to viral HA. Here we studied the molecular interactions between Ncr1 and influenza viruses. We show that Ncr1 recognizes influenza virus in a sialic acid dependent manner and that N-glycosylation is important for this binding. Surprisingly we demonstrate that none of the predicted N-glycosilated residues of Ncr1 are essential for its binding to influenza virus and we thus conclude that other, yet unidentified N-glycosilated residues are responsible for its recognition. We have demonstrated that N glycosylation play little role in the recognition of mouse tumor cell lines and also showed the in-vivo importance of Ncr1 in the control of influenza virus infection by infecting C57BL/6 and BALB/c mice knockout for Ncr1 with influenza.