Showing papers by "University of Rijeka published in 2010"
TL;DR: The evidence has been accumulated supporting the role of viral immunoevasion of NK cells in viral pathogenesis in vivo and the existence of plethora of viral mechanisms aimed to modulate their function.
1,081 citations
University of Westminster1, University of Tartu2, Pontifical Catholic University of Chile3, University of Otago4, Islamic University of Indonesia5, Himalayan Institute of Yoga Science and Philosophy6, International Institute for Applied Systems Analysis7, Macquarie University8, Polish Academy of Sciences9, Millikin University10, University College London11, King's College London12, University of Vienna13, Kyung Hee University14, Hope College15, University of Malaya16, University of Delaware17, Kocaeli University18, Chemnitz University of Technology19, University of KwaZulu-Natal20, University of Texas at Austin21, University of Idaho22, University of Helsinki23, University of California, Los Angeles24, University of Regina25, Deakin University26, Brock University27, Florida Atlantic University28, University of Porto29, Ateneo de Manila University30, University of Rijeka31, University of Zurich32, Ghent University33, University of Wrocław34, National University of Malaysia35, Loughborough University36
TL;DR: Results indicated there were significant cross-regional differences in the ideal female figure and body dissatisfaction, but effect sizes were small across high-socioeconomic-status (SES) sites.
Abstract: This study reports results from the first International Body Project (IBP-I), which surveyed 7,434 individuals in 10 major world regions about body weight ideals and body dissatisfaction. Participants completed the female Contour Drawing Figure Rating Scale (CDFRS) and self-reported their exposure to Western and local media. Results indicated there were significant cross-regional differences in the ideal female figure and body dissatisfaction, but effect sizes were small across high-socioeconomic-status (SES) sites. Within cultures, heavier bodies were preferred in low-SES sites compared to high-SES sites in Malaysia and South Africa (ds = 1.94-2.49) but not in Austria. Participant age, body mass index (BMI), and Western media exposure predicted body weight ideals. BMI and Western media exposure predicted body dissatisfaction among women. Our results show that body dissatisfaction and desire for thinness is commonplace in high-SES settings across world regions, highlighting the need for international attention to this problem.
584 citations
TL;DR: In this paper, the authors presented the first measurement of the planet frequency beyond the "snow line," for the planet-to-star mass-ratio interval during 2005-2008 microlensing events during the survey-plus-follow-up high-magnification channel.
Abstract: We present the first measurement of the planet frequency beyond the "snow line," for the planet-to-star mass-ratio interval –4.5 200) microlensing events during 2005-2008. The sampled host stars have a typical mass M_(host) ~ 0.5 M_⊙, and detection is sensitive to planets over a range of planet-star-projected separations (s ^(–1)_(max)R_E, s_(max)R_E), where R_E ~ 3.5 AU(M_(host)/M_⊙)^(1/2) is the Einstein radius and s_(max) ~ (q/10^(–4.3))^(1/3). This corresponds to deprojected separations roughly three times the "snow line." We show that the observations of these events have the properties of a "controlled experiment," which is what permits measurement of absolute planet frequency. High-magnification events are rare, but the survey-plus-follow-up high-magnification channel is very efficient: half of all high-mag events were successfully monitored and half of these yielded planet detections. The extremely high sensitivity of high-mag events leads to a policy of monitoring them as intensively as possible, independent of whether they show evidence of planets. This is what allows us to construct an unbiased sample. The planet frequency derived from microlensing is a factor 8 larger than the one derived from Doppler studies at factor ~25 smaller star-planet separations (i.e., periods 2-2000 days). However, this difference is basically consistent with the gradient derived from Doppler studies (when extrapolated well beyond the separations from which it is measured). This suggests a universal separation distribution across 2 dex in planet-star separation, 2 dex in mass ratio, and 0.3 dex in host mass. Finally, if all planetary systems were "analogs" of the solar system, our sample would have yielded 18.2 planets (11.4 "Jupiters," 6.4 "Saturns," 0.3 "Uranuses," 0.2 "Neptunes") including 6.1 systems with two or more planet detections. This compares to six planets including one two-planet system in the actual sample, implying a first estimate of 1/6 for the frequency of solar-like systems.
381 citations
Nagoya University1, University of Notre Dame2, Massey University3, University of Warsaw4, Royal Society5, University of St Andrews6, Centre national de la recherche scientifique7, Ohio State University8, Lawrence Livermore National Laboratory9, Institute for Advanced Study10, University of Auckland11, University of Canterbury12, Victoria University of Wellington13, Konan University14, College of Industrial Technology15, Institut d'Astrophysique de Paris16, University of Tasmania17, University of Chile18, National Institute for Space Research19, Liverpool John Moores University20, European Southern Observatory21, Ames Research Center22, University of Stuttgart23, University of the Free State24, University of Rijeka25, University of Vienna26, Niels Bohr Institute27, NASA Exoplanet Science Institute28, Space Telescope Science Institute29, Las Cumbres Observatory Global Telescope Network30, Heidelberg University31, University of Concepción32, Texas A&M University33, Chungbuk National University34, Korea Astronomy and Space Science Institute35, Auckland University of Technology36
TL;DR: The OGLE-2007-BLG-368Lb with a planet-star mass ratio of q = [9.5 ± 2.1] × 10^(-5] via gravitational microlensing was discovered in real-time thanks to the high cadence of the Microlensing Observations in Astrophysics survey and intensive followup observations.
Abstract: We present the discovery of a Neptune-mass planet OGLE-2007-BLG-368Lb with a planet-star mass ratio of q = [9.5 ± 2.1] × 10^(-5) via gravitational microlensing. The planetary deviation was detected in real-time thanks to the high cadence of the Microlensing Observations in Astrophysics survey, real-time light-curve monitoring and intensive follow-up observations. A Bayesian analysis returns the stellar mass and distance at M_l = 0.64^(+0.21)_(–0.26) M_☉ and D_l = 5.9^(+0.9)_(–1.4) kpc, respectively, so the mass and separation of the planet are M_p = 20^(+7)_(–8) M_⊕ and a = 3.3^(+1.4)_(–0.8) AU, respectively. This discovery adds another cold Neptune-mass planet to the planetary sample discovered by microlensing, which now comprises four cold Neptune/super-Earths, five gas giant planets, and another sub-Saturn mass planet whose nature is unclear. The discovery of these 10 cold exoplanets by the microlensing method implies that the mass ratio function of cold exoplanets scales as dN_(pl)/d log q ∝ q^(–0.7±0.2) with a 95% confidence level upper limit of n < –0.35 (where dN_(pl)/d log q ∝ q^n). As microlensing is most sensitive to planets beyond the snow-line, this implies that Neptune-mass planets are at least three times more common than Jupiters in this region at the 95% confidence level.
253 citations
TL;DR: In this article, the authors investigated relations among strengths of character in 881 students from Croatian universities and examined links between strengths and various well-being indices, finding that vitality (with zest, hope, curiosity, gratitude, and optimism/hope) emerged with the strongest associations with elevated life satisfaction, subjective vitality, satisfaction of autonomy, relatedness, and competence needs, and a pleasurable, engaging, and meaningful existence.
216 citations
TL;DR: Long-range magnitude cross-correlations in collective modes of real-world data from finance, physiology, and genomics using time-lag random matrix theory are found, indicating scale-invariant interactions between different physiological time series.
Abstract: We study long-range magnitude cross-correlations in collective modes of real-world data from finance, physiology, and genomics using time-lag random matrix theory. We find long-range magnitude cross-correlations i) in time series of price fluctuations, ii) in physiological time series, both healthy and pathological, indicating scale-invariant interactions between different physiological time series, and iii) in ChIP-seq data of the mouse genome, where we uncover a complex interplay of different DNA-binding proteins, resulting in power-law cross-correlations in xij, the probability that protein i binds to gene j, ranging up to 10 million base pairs. In finance, we find that the changes in singular vectors and singular values are largest in times of crisis. We find that the largest 500 singular values of the NYSE Composite members follow a Zipf distribution with exponent ≈2. In physiology, we find statistically significant differences between alcoholic and control subjects.
210 citations
01 Jan 2010-Microsystem Technologies-micro-and Nanosystems-information Storage and Processing Systems
TL;DR: In this article, the shape of scavengers is optimized to increase the specific power generated per unit of scavenger volume by optimizing shape of the scavengers, and two optimized trapezoidal configurations are identified and analyzed.
Abstract: Compact autonomous power sources are one of the prerequisites for the development of wireless sensor networks. In this work vibration energy harvesting via piezoelectric resonant bimorph beams is studied. The available analytical approaches for the modeling of the coupled electromechanical behavior are critically evaluated and compared with a finite element (FEM) numerical model. The latter is applied to analyze thoroughly the stress and strain states, as well as to evaluate the resulting voltage and charge distributions in the piezoelectric layers. The aim of increasing the specific power generated per unit of scavenger volume is pursued by optimizing the shape of the scavengers. Two optimized trapezoidal configurations are hence identified and analyzed. An experimental set-up for the validation of the proposed numerical model and of the obtained optimized structures is developed. Results of a preliminary experimental assessment, confirming the improved performances of optimized scavengers, are finally given.
177 citations
TL;DR: The MAGIC Cherenkov telescope was used to observe the Perseus galaxy cluster for a total effective time of 24.4 hours during 2008 November and December as discussed by the authors, and the resulting upper limits on the gamma-ray emission above 100 GeV are in the range of 4.6-7.5, thereby constraining the emission produced by cosmic rays, dark matter annihilations and the central radio galaxy NGC 1275.
Abstract: The Perseus galaxy cluster was observed by the MAGIC Cherenkov telescope for a total effective time of 24.4 hr during 2008 November and December. The resulting upper limits on the gamma-ray emission above 100 GeV are in the range of 4.6-7.5 x 10(-12) cm(-2) s(-1) for spectral indices from -1.5 to -2.5, thereby constraining the emission produced by cosmic rays, dark matter annihilations, and the central radio galaxy NGC 1275. Results are compatible with cosmological cluster simulations for the cosmic-ray-induced gamma-ray emission, constraining the average cosmic ray-to-thermal pressure to < 4% for the cluster core region (< 8% for the entire cluster).
162 citations
TL;DR: The psychometric characteristics of the EORTC INFO module in a large international/multi-cultural sample of cancer patients found it to be a reliable and valid self-reported instrument that can be used in cross-cultural observational and intervention studies.
162 citations
TL;DR: Docking study showed that flavonoids bind to the BChE active site by forming multiple hydrogen bonds and pi-pi interactions, and UV-VIS absorption spectra of the flavonoid phosphate buffer solution revealed time dependant changes indicating precipitation of Flavonoids or in the case of myricetin, a change in the chemical structure resulting in a BChChE non-inhibiting specie.
150 citations
TL;DR: It is highlighted that tumoral mucin-mediated ligation of the MR on infiltrating TAM may contribute to their immune suppressive phenotype.
Abstract: Tumor-Associated Macrophages (TAMs) are abundantly present in the stroma of solid tumors and modulate several important biological processes, such as neoangiogenesis, cancer cell proliferation and invasion, and suppression of adaptive immune responses. Myeloid C-type lectin receptors (CLRs) constitute a large family of transmembrane carbohydrate-binding receptors that recognize pathogens as well as endogenous glycoproteins. Several lines of evidence demonstrate that some CLRs can inhibit the immune response. In this study we investigated TAM-associated molecules potentially involved in their immune suppressive activity. We found that TAMs isolated from human ovarian carcinoma samples predominantly express the CLRs Dectin-1, MDL-1, MGL, DCIR, and most abundantly the Mannose Receptor (MR). Components of carcinomatous ascites and purified tumoral mucins (CA125 and TAG-72) bound the MR and induced its internalization. MR engagement by tumoral mucins and by an agonist anti-MR antibody modulated cytokine production by TAM toward an immune-suppressive profile: increase of IL-10, absence of IL-12, and decrease of the Th1-attracting chemokine CCL3. This study highlights that tumoral mucin-mediated ligation of the MR on infiltrating TAM may contribute to their immune suppressive phenotype.
TL;DR: This study shows novel localized recruitment of the host farnesylation machinery and its anchoring of an F-box effector to the LCV membrane, and this is essential for biological function in vitro and in vivo.
Abstract: Farnesylation involves covalent linkage of eukaryotic proteins to a lipid moiety to anchor them into membranes, which is essential for the biological function of Ras and other proteins. A large cadre of bacterial effectors is injected into host cells by intravacuolar pathogens through elaborate type III–VII translocation machineries, and many of these effectors are incorporated into the pathogen-containing vacuolar membrane by unknown mechanisms. The Dot/Icm type IV secretion system of Legionella pneumophila injects into host cells the F-box effector Ankyrin B (AnkB), which functions as platforms for the docking of polyubiquitinated proteins to the Legionella-containing vacuole (LCV) to enable intravacuolar proliferation in macrophages and amoeba. We show that farnesylation of AnkB is indispensable for its anchoring to the cytosolic face of the LCV membrane, for its biological function within macrophages and Dictyostelium discoideum, and for intrapulmonary proliferation in mice. Remarkably, the protein farnesyltransferase, RCE-1 (Ras-converting enzyme-1), and isoprenyl cysteine carboxyl methyltransferase host farnesylation enzymes are recruited to the LCV in a Dot/Icm-dependent manner and are essential for the biological function of AnkB. In conclusion, this study shows novel localized recruitment of the host farnesylation machinery and its anchoring of an F-box effector to the LCV membrane, and this is essential for biological function in vitro and in vivo.
TL;DR: In this article, the effect of ultrasound and sonication on α-lactalbumin (α-LA) with a view to improving its physicochemical and functional properties was examined.
Abstract: Ultrasound is the sound whose frequency is too high for humans to hear which is within the frequency range of 20 Hz–20 kHz, and the frequency of ultrasound is above 20 kHz. The aim of this study was to observe the effect of ultrasound and sonication on α-lactalbumin (α-LA) with a view to improving its physicochemical and functional properties. In this work both low-intensity ultrasound (500 kHz bath) and the high-intensity ultrasound (20 kHz probe and 40 kHz bath) were used. Ten per cent wt (g g−1 dry matter) protein model suspensions of α-lactalbumin (α-LA) were treated with ultrasound probe (20 kHz for 15 and 30 min) and ultrasound baths (40 kHz and 500 kHz for 15 and 30 min). Changes in pH values, electrical conductivity, solubility measurements, foaming properties, as well as rheological and freezing-thawing properties have been examined. The protein fractions of α-lactalbumin were analyzed before and after ultrasound treatment by SDS-PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis). The result showed that pH did not change significantly upon ultrasound however conductivities increased significantly after 20 kHz sonication. Electrical conductivity decreased significantly for ultrasound treatments in baths at 40 kHz and 500 kHz for all samples. Solubility increased significantly for all samples at 20 kHz. Foam capacities and foam stabilities were improved after ultrasound treatments for both 20 kHz and 40 kHz treatments. Foaming properties were not improved for protein model suspensions for 500 kHz treatments. The molecular weight of the protein decreased significantly after ultrasound treatments both using a 20 kHz probe and 40 kHz bath. The flow behaviour of α-lactalbumin was observed to be shear-thickening after all treatments. Apparent viscosity data calculated with power law equation (R2 = 0.983–0.999) have not been changed significantly after all treatments. A remarkable decrease of initial freezing point was obtained after 20 kHz treatments.
TL;DR: In this article, the MAGIC telescopes were used to detect very high energy (VHE) gamma-rays from IC 310, a head-tail radio galaxy in the Perseus galaxy cluster, observed during the interval 2008 November to 2010 February.
Abstract: We report on the detection with the MAGIC telescopes of very high energy (VHE) gamma-rays from IC 310, a head-tail radio galaxy in the Perseus galaxy cluster, observed during the interval 2008 November to 2010 February. The Fermi satellite has also detected this galaxy. The source is detected by MAGIC at a high statistical significance of 7.6 sigma in 20.6 hr of stereo data. The observed spectral energy distribution is flat with a differential spectral index of -2.00 +/- 0.14. The mean flux above 300 GeV, between 2009 October and 2010 February, (3.1 +/- 0.5) x 10(-12) cm(-2) s(-1), corresponds to (2.5 +/- 0.4)% of Crab Nebula units. Only an upper limit, of 1.9% of Crab Nebula units above 300 GeV, was obtained with the 2008 data. This, together with strong hints (>3 sigma) of flares in the middle of 2009 October and November, implies that the emission is variable. The MAGIC results favor a scenario with the VHE emission originating from the inner jet close to the central engine. More complicated models than a simple one-zone synchrotron self-Compton (SSC) scenario, e. g., multi-zone SSC, external Compton, or hadronic, may be required to explain the very flat spectrum and its extension over more than three orders of magnitude in energy.
TL;DR: In this article, the MAGIC telescopes were used to detect very high energy gamma-rays from IC 310, a head-tail radio galaxy in the Perseus galaxy cluster, observed during the interval November 2008 to February 2010.
Abstract: We report on the detection with the MAGIC telescopes of very high energy gamma-rays from IC 310, a head-tail radio galaxy in the Perseus galaxy cluster, observed during the interval November 2008 to February 2010. The Fermi satellite has also detected this galaxy. The source is detected by MAGIC at a high statistical significance of 7.6sigma in 20.6 hr of stereo data. The observed spectral energy distribution is flat with a differential spectral index of -2.00 \pm 0.14. The mean flux above 300 GeV, between October 2009 and February 2010, (3.1 \pm 0.5)x10^{-12} cm^{-2} s^{-1}, corresponds to (2.5 \pm 0.4)% of Crab Nebula units. Only an upper limit, of 1.9% of Crab Nebula units above 300 GeV, was obtained with the 2008 data. This, together with strong hints (>3sigma) of flares in the middle of October and November 2009, implies that the emission is variable. The MAGIC results favour a scenario with the very high energy emission originating from the inner jet close to the central engine. More complicated models than a simple one-zone SSC scenario, e.g. multi-zone SSC, external Compton or hadronic, may be required to explain the very flat spectrum and its extension over more than three orders of magnitude in energy.
TL;DR: In this paper, the authors assess customers' expectations and perceptions, establish the significance of difference between perceived and expected service quality, and test the reliability of the applied DINESERV model.
Abstract: The purpose of this study is to determine restaurant service quality. The aims are to: (a) assess customers’ expectations and perceptions, (b) establish the significance of difference between perceived and expected service quality, (c) identify the number of dimensions for expectations and perceptions scales of modified DINESERV model, (d) test the reliability of the applied DINESERV model. The empirical research was conducted using primary data. The questionnaire is based on Stevens et al. (1995) and Andaleeb and Conway’s (2006) research. In order to meet survey goals, descriptive, bivariate and multivariate (exploratory factor analysis and reliability analysis) statistical analyses were conducted. The empirical results show that expectations scores are higher than perceptions scores, which indicate low level of service quality. Furthermore, this study identified seven factors that best explain customers’ expectations and two factors that best explain customers’ perceptions regarding restaurant service. The results of this study would help management identify the strengths and weaknesses of service quality and implement an effective strategy to meet the customers’ expectations.
TL;DR: The past few years have witnessed a quantum leap in understanding of various aspects of this organism and this review will discuss these remarkable advances.
Abstract: Francisella tularensis is a highly infectious intracellular bacterium that causes the fulminating disease tularemia, which can be transmitted between mammals by arthropod vectors. Genomic studies have shown that the F. tularensis has been undergoing genomic decay with the most virulent strains having the lowest number of functional genes. Entry of F. tularensis into macrophages is mediated by looping phagocytosis and is associated with signalling through Syk tyrosine kinase. Within macrophages and arthropod-derived cells, the Francisella-containing phagosome matures transiently into an acidified late endosome-like phagosome with limited fusion to lysosomes followed by rapid bacterial escape into the cytosol within 30-60 min, and bacterial proliferation within the cytosol. The Francisella pathogenicity island, which potentially encodes a putative type VI secretion system, is essential for phagosome biogenesis and bacterial escape into the cytosol within macrophages and arthropod-derived cells. Initial sensing of F. tularensis in the cytosol triggers IRF-3-dependent IFN-beta secretion, type I IFNR-dependent signalling, activation of the inflammasome mediated by caspase-1, and a pro-inflammatory response, which is suppressed by triggering of SHIP. The past few years have witnessed a quantum leap in our understanding of various aspects of this organism and this review will discuss these remarkable advances.
TL;DR: Nuclear EGFR was revealed to be an independent prognostic factor and showed 3.4 times greater mortality risk for nuclear EGFR+++ patients as compared withnuclear EGFR negative patients (hazard ratio =3.4; P=0.402) and cyclin-D1 expression showed a correlation with longer overall survival in the premenopausal group and nuclear EG FR correlated with shorter overall life expectancy in whole cohort as well in thePremenopausal Group of patients.
24 Nov 2010
TL;DR: Formation of nitrogen vacancies under low-energy ion bombardment reduces oxidation resistance of BN structures and promotes an efficient oxygen-healing mechanism, in full agreement with some recent theoretical predictions.
Abstract: Decoration of nitrogen vacancies by oxygen atoms has been studied by near-edge x-ray absorption fine structure (NEXAFS) in several boron nitride (BN) structures, including bamboo-like and multi-walled BN nanotubes. Formation of nitrogen vacancies under low-energy ion bombardment reduces oxidation resistance of BN structures and promotes an efficient oxygen-healing mechanism, in full agreement with some recent theoretical predictions.
TL;DR: Natural killer cell recognition of “missing self” contributes meaningfully to control of mouse cytomegalovirus infection in vivo.
Abstract: Cytomegaloviruses (CMVs) are renowned for interfering with the immune system of their hosts. To sidestep antigen presentation and destruction by CD8+ T cells, these viruses reduce expression of major histocompatibility complex class I (MHC I) molecules. However, this process sensitizes the virus-infected cells to natural killer (NK) cell–mediated killing via the “missing self” axis. Mouse cytomegalovirus (MCMV) uses m152 and m06 encoded proteins to inhibit surface expression of MHC I molecules. In addition, it encodes another protein, m04, which forms complexes with MHC I and escorts them to the cell surface. This mechanism is believed to prevent NK cell activation and killing by restoring the “self” signature and allowing the engagement of inhibitory Ly49 receptors on NK cells. Here we show that MCMV lacking m04 was attenuated in an NK cell– and MHC I–dependent manner. NK cell–mediated control of the infection was dependent on the presence of NK cell subsets expressing different inhibitory Ly49 receptors. In addition to providing evidence for immunoevasion strategies used by CMVs to avoid NK cell control via the missing-self pathway, our study is the first to demonstrate that missing self–dependent NK cell activation is biologically relevant in the protection against viral infection in vivo.
TL;DR: The results indicate that use of a recombinant virus encoding the ligand for an activating NK cell receptor could be a powerful approach to developing a safe and immunogenic HCMV vaccine.
Abstract: Human CMV (HCMV) is a major cause of morbidity and mortality in both congenitally infected and immunocompromised individuals. Development of an effective HCMV vaccine would help protect these vulnerable groups. NK group 2, member D (NKG2D) is a potent activating receptor expressed by cells of the innate and adaptive immune systems. Its importance in HCMV immune surveillance is indicated by the elaborative evasion mechanisms evolved by the virus to avoid NKG2D. In order to study this signaling pathway, we engineered a recombinant mouse CMV expressing the high-affinity NKG2D ligand RAE-1γ (RAE-1γMCMV). Expression of RAE-1γ by MCMV resulted in profound virus attenuation in vivo and lower latent viral DNA loads. RAE-1γMCMV infection was efficiently controlled by immunodeficient hosts, including mice lacking type I interferon receptors or immunosuppressed by sublethal γ-irradiation. Features of MCMV infection in neonates were also diminished. Despite tight innate immune control, RAE-1γMCMV infection elicited strong and long-lasting protective immunity. Maternal RAE-1γMCMV immunization protected neonatal mice from MCMV disease via placental transfer of antiviral Abs. Despite strong selective pressure, the RAE-1γ transgene did not exhibit sequence variation following infection. Together, our results indicate that use of a recombinant virus encoding the ligand for an activating NK cell receptor could be a powerful approach to developing a safe and immunogenic HCMV vaccine.
TL;DR: During subacute infection of a mutant mouse cytomegalovirus lacking two viral miRNAs, virus production is selectively reduced in salivary glands, an organ essential for virus persistence and horizontal transmission, pointing towards a miRNA-based immunoevasion mechanism important for long-term virus persistence.
Abstract: Micro (mi)RNAs are small non-coding RNAs that regulate the expression of their targets' messenger RNAs through both translational inhibition and regulation of target RNA stability. Recently, a number of viruses, particularly of the herpesvirus family, have been shown to express their own miRNAs to control both viral and cellular transcripts. Although some targets of viral miRNAs are known, their function in a physiologically relevant infection remains to be elucidated. As such, no in vivo phenotype of a viral miRNA knock-out mutant has been described so far. Here, we report on the first functional phenotype of a miRNA knock-out virus in vivo. During subacute infection of a mutant mouse cytomegalovirus lacking two viral miRNAs, virus production is selectively reduced in salivary glands, an organ essential for virus persistence and horizontal transmission. This phenotype depends on several parameters including viral load and mouse genetic background, and is abolished by combined but not single depletion of natural killer (NK) and CD4+ T cells. Together, our results point towards a miRNA-based immunoevasion mechanism important for long-term virus persistence.
TL;DR: In this paper, an analysis of a few tens of hours of observational data taken from Mrk 421 and Mrk 501 using a newly developed method that provides better angular resolution is presented.
Abstract: Context. Part of the very high energy -ray radiation coming from extragalactic sources is absorbed through the pair production process on the extragalactic background light photons. Extragalacti c magnetic fields alter the trajectories of these cascade pai rs and, in turn, convert cosmic background photons to gamma-ray energies by inverse Compton scattering. These secondary photons can form an extended halo around bright VHE sources. Aims. We searched for an extended emission around the bright blazars Mrk 421 and Mrk 501 using the MAGIC telescope data. Methods. If extended emission is present, the angular distribution o f reconstructed gamma-ray arrival directions around the source is broader than for a point-like source. In the analysis of a few tens of hours of observational data taken from Mrk 421 and Mrk 501 we used a newly developed method that provides better angular resolution. This method is based on the usage of multidimensional decision trees. Comparing the measured shapes of angular distributions with those expected from a point-like source one can detect or constrain possible exten ded emission around the source. We also studied the influence of di fferent types of systematic errors on the shape of the distribu tion of reconstructed gamma-ray arrival directions for a point source. Results. We present upper limits for an extended emission calculated for both sources for various source extensions and emission profiles. We obtain upper limits on the extended emission around the Mrk 421 (Mrk 501) on the level of < 5% (< 4% ) of the Crab Nebula flux above the energy threshold of 300 GeV. Using these results we discuss possible constraints on the extragalactic magnetic fields st rength around a few times 10 −15 G.
TL;DR: An on-line HPLC–MS method for phospholipid profiling in the CSF based on nano-HPLC separation using an Amide column and detection with electrospray (ESI) quadrupole–time of flight (QTOF) MS is developed and observed a statistically significant increase of SM levels.
Abstract: There is emerging evidence that lipids play an important role in many neurodegenerative processes, for example in Alzheimer’s disease (AD). Although different lipid alterations in the AD brain have been reported, there have only been very few investigations of lipid changes in the cerebrospinal fluid (CSF). Recent developments in mass spectrometry (MS) have enabled fast and sensitive detection of lipid species in different biological matrixes. In this study we developed an on-line HPLC–MS method for phospholipid profiling in the CSF based on nano-HPLC separation using an Amide column and detection with electrospray (ESI) quadrupole–time of flight (QTOF) MS. We achieved good separation, reproducibility, and sensitivity in monitoring of the major phospholipid classes, phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidylinositol (PI), and sphingomyelin (SM) in CSF. To emphasize the applicability of the method, a pilot study was performed on a group of CSF samples (N = 16) from individuals with probable AD and non-demented controls. We observed a statistically significant increase of SM levels (24.3 ± 2.4%) in CSF from probable AD individuals vs. controls. Our findings indicate that SM levels in the CSF could potentially provide a new lead in AD biomarker research, and show the potential of the method for disease-associated CSF phospholipid screening.
TL;DR: The results suggest the therapeutic effect of DWE on CCl(4)-induced liver fibrosis by the inactivation of hepatic stellate cells and the enhancement of liver regenerative capabilities.
TL;DR: This article shows that CD300a is indeed an inhibitory receptor expressed by human NK cells, but surprisingly, it is shown that not all NK clones are inhibited in aCD300a-dependent manner.
Abstract: The killing activity of NK cells is regulated by signals derived from inhibitory and activating NK cell receptors, including the CD300 family of proteins. CD300a was reported to be expressed on all NK cells and to deliver an inhibitory signal upon binding to a yet unknown ligand/s. The CD300a protein contains four ITIMs and is highly homologous to CD300c. Little is known about the function and distribution of these two receptors and the identity of their ligand/s. In this article, we show that CD300a is indeed an inhibitory receptor expressed by human NK cells, but surprisingly, we show that not all NK clones are inhibited in a CD300a-dependent manner. We demonstrate, using a panel of 13 new anti-CD300a and CD300c Abs that we generated, that CD300a and CD300c are indistinguishable on the surface of NK cells. Using mutational-analysis survey, we show that tyrosine 267 located in the third ITIM motif of the CD300a protein is important for the inhibitory function of CD300a.
TL;DR: The data, in combination with a report by others show that the TLR2‐P631H allele could be associated with protection to meningococcal meningitis, suggest that by dominantly inhibiting the response of cells important in the immune response this mutant might confer either protection or susceptibility toMeningitis or tuberculosis, respectively.
Abstract: We have sequenced 416 Toll-like receptor-2 (TLR2) alleles in 208 subjects in a tuberculosis case–control study in Croatian Caucasian population. We found ten single nucleotide polymorphisms (SNP) among which three were novel (S97S, T138I and L266F). The genotype containing TLR2-P631H SNP was significantly overrepresented in patients with tuberculosis when compared to contact controls, suggesting a small yet increased risk to disease. The causative agent of tuberculosis is Mycobacterium tuberculosis, which can bind to TLR2 with its lipoprotein coat. The TLR2-P631H mutant has a dominant negative effect on the wild type TLR2 signalling in transfected HEK293 kidney cells using the NF-κB-driven luciferase as a reporter gene with ligands like M. avium extracts, Pam3CysSK4 or FSL-1 that bind TLR2/TLR1 or TLR2/TLR6 heterodimers, respectively. Studies on internalization from the Regular Madine Darby Canine Kidney cell surface into the early endosomal compartments showed a lower rate of the mutant compared to the wild type. Our data, in combination with a report by others show that the TLR2-P631H allele could be associated with protection to meningococcal meningitis, suggest that by dominantly inhibiting the response of cells important in the immune response this mutant might confer either protection or susceptibility to meningitis or tuberculosis, respectively.
TL;DR: Use of a spread-deficient murine CMV (MCMV) as a novel approach for betaherpesvirus vaccination is described and the linkage between cell tropism and immunogenicity is allowed.
Abstract: Human cytomegalovirus (HCMV) is a human pathogen that causes severe disease primarily in the immunocompromised or immunologically immature individual. To date, no vaccine is available. We describe use of a spread-deficient murine CMV (MCMV) as a novel approach for betaherpesvirus vaccination. To generate a spread-deficient MCMV, the conserved, essential gene M94 was deleted. Immunization with MCMV-DeltaM94 is apathogenic and protective against wild-type challenge even in highly susceptible IFNalphabetaR(-/-) mice. MCMV-DeltaM94 was able to induce a robust CD4(+) and CD8(+) T-cell response as well as a neutralizing antibody response comparable to that induced by wild-type infection. Endothelial cells were identified as activators of CD8(+) T cells in vivo. Thus, the vaccination with a spread-deficient betaherpesvirus is a safe and protective strategy and allows the linkage between cell tropism and immunogenicity. Furthermore, genomes of MCMV-DeltaM94 were present in lungs 12 months after infection, revealing first-target cells as sites of genome maintenance.
TL;DR: The findings of this study show that malocclusion has more impact on emotional well-being than on function or social contacts and that Malocclusion-related quality of life was poorly associated with treatment need.
Abstract: Patients’ and parents’ perception of malocclusion are important in determining orthodontic treatment demand, motivation, and cooperation. The aim of this study was to investigate differences in perception of treatment need in currently orthodontically treated, previously treated, and untreated subjects.
The sample comprised 3196 children and adolescents (1593 males and 1603 females) aged 8–19 years (mean age 13.0 ± 3.6 years) from 24 randomly selected public schools in Zagreb, Croatia. Objective treatment need was assessed clinically using the Dental Aesthetic Index (DAI). Subjective treatment need was estimated separately by an orthodontic resident, the child/adolescent and his/her parent using the Standardized Continuum of Aesthetic Need (SCAN) procedure. The children/adolescents completed a questionnaire that had five questions with five-point Likert-type scale answers concerning satisfaction with dental appearance, importance of teeth for facial appearance, and malocclusion-related quality of life. Spearman correlation and logistic regression were used for statistical analysis.
Associations between objective and subjective orthodontic treatment need were weak but statistically significant (Rho from 0.20 to 0.50; P < 0.05). Malocclusion-related quality of life was poorly associated with treatment need. Satisfaction with tooth appearance showed the most frequent statistically significant correlation (Rho from −0.14 to −0.35; P < 0.05), while importance of aligned teeth for facial appearance and social contacts had the weakest correlation with treatment need. Perception of treatment need was greater in previously treated subjects. Parents’ perception had a low predictive value.
The findings of this study show that malocclusion has more impact on emotional well-being than on function or social contacts.
TL;DR: The Major Atmospheric Gamma Imaging Cerenkov (MAGIC) telescope participated in three multi-wavelength (MWL) campaigns, observing the blazar Markarian (Mkn) 421 during the nights of April 28 and 29, 2006, and June 14, 2006.
Abstract: Context. Wide-range spectral coverage of blazar-type active galactic nuclei is of paramount importance for understanding the particle acceleration mechanisms assumed to take place in their jets. The Major Atmospheric Gamma Imaging Cerenkov (MAGIC) telescope participated in three multiwavelength (MWL) campaigns, observing the blazar Markarian (Mkn) 421 during the nights of April 28 and 29, 2006, and June 14, 2006. Aims. We analyzed the corresponding MAGIC very-high energy observations during 9 nights from April 22 to 30, 2006 and on June 14, 2006. We inferred light curves with sub-day resolution and night-by-night energy spectra. Methods. MAGIC detects gamma-rays by observing extended air showers in the atmosphere. The obtained air-shower images were analyzed using the standard MAGIC analysis chain. Results. A strong gamma-ray signal was detected from Mkn 421 on all observation nights. The flux (E > 250 GeV) varied on night-by-night basis between (0.92 +/- 0.11) x 10(-10) cm(-2) s(-1) (0.57 Crab units) and (3.21 +/- 0.15) x 10(-10) cm(-2) s(-1) (2.0 Crab units) in April 2006. There is a clear indication for intra-night variability with a doubling time of 36 +/- 10(stat) min on the night of April 29, 2006, establishing once more rapid flux variability for this object. For all individual nights gamma-ray spectra could be inferred, with power-law indices ranging from 1.66 to 2.47. We did not find statistically significant correlations between the spectral index and the flux state for individual nights. During the June 2006 campaign, a flux substantially lower than the one measured by the Whipple 10-m telescope four days later was found. Using a log-parabolic power law fit we deduced for some data sets the location of the spectral peak in the very-high energy regime. Our results confirm the indications of rising peak energy with increasing flux, as expected in leptonic acceleration models.