Regulation of NO production by MAPK dual-specificity phosphatases (DUSP) in human neutrophils exposed to N-nitrosodimethylamine

437-444One of the enzymes responsible for nitric oxide (NO) production in neutrophils is the inducible nitric oxide synthase (iNOS). Changes in its expression may result from the activation of different signaling pathways, including MAPK, which lead to activation of various genes, including DUSP genes. DUSP induce the negative feedback loop leading to MAPK deactivation through their phosphorylation. Our study assessed the role of DUSP1, DUSP10 and DUSP16 with the participation of MAPK in the iNOS-dependent NO production by neutrophils exposed to xenobiotic, N-nitrosodimethylamine (NDMA). The obtained results suggest that N-nitrosodimethylamine enhances the expression of all tested proteins (except DUSP10) in the cytoplasmic and nuclear fractions of neutrophils. The JNK pathway inhibition resulted in an extenuation of iNOS, phospho-p38 and DUSP10 expression in the cytoplasmic fraction and DUSP1 expression in the nuclear fraction of neutrophils. Inhibition of the p38 pathway led to a lower expression of iNOS, DUSP16 and DUSP10 in the cytoplasmic fraction. No changes in the phospho-JNK and DUSP1 expressions were observed. With the results of this study we can conclude that DUSP are positive regulators of MAP kinases in NDMA-induced signaling pathway which lead to modulation of iNOS-dependent NO production in human neutrophils

Candidates for Transiting Planets in OGLE-IV Galactic Bulge Fields

We present results of a search for transiting exoplanets in 10-yr long photometry with thousands of epochs taken in the direction of the Galactic bulge. This photometry was collected in the fourth phase of the Optical Gravitational Lensing Experiment (OGLE-IV). Our search covered approx. 222 000 stars brighter than I = 15.5 mag. Selected transits were verified using a probabilistic method. The search resulted in 99 high-probability candidates for transiting exoplanets. The estimated distances to these targets are between 0.4 kpc and 5.5 kpc, which is a significantly wider range than for previous transit searches. The planets found are Jupiter-size, with the exception of one (named OGLE-TR-1003b) located in the hot Neptune desert. If the candidate is confirmed, it can be important for studies of highly irradiated intermediate-size planets. The existing long-term, high-cadence photometry of our candidates increases the chances of detecting transit timing variations at long timescales. Selected candidates will be observed by the future NASA flagship mission, the Nancy Grace Roman Space Telescope, in its search for Galactic bulge microlensing events, which will further enhance the photometric coverage of these stars.Comment: 35 pages, 13 figures, 4 tables. Published in Acta Astronomica, online catalog: https://ogledb.astrouw.edu.pl/~ogle/OCVS

The OGLE Collection of Variable Stars. One Thousand Heartbeat Stars in the Galactic Bulge and Magellanic Clouds

We present a collection of 991 heartbeat star (HBS) candidates found in the Optical Gravitational Lensing Experiment (OGLE) project data archive. We discuss the selection process of the HBS candidates and the structure of the catalog itself. It consists of 512 stars located toward the Galactic bulge (GB), 439 stars located in the Large Magellanic Cloud (LMC), and 40 in the Small Magellanic Cloud (SMC). The collection contains two large groups of HBSs with different physical properties. The main distinction between the two groups is the evolutionary status of the primary star. The first group of about 100 systems contains a hot main-sequence (MS) or a Hertzsprung-gap primary star, while the second group of about 900 systems includes a red giant (RG). For each star, we provide two-decade-long time-series photometry, in the Cousins $I$- and Johnson $V$-band filters, obtained by the OGLE project. We also present basic observational information as well as orbital parameters derived from the light curve modeling.Comment: 15 pages, 10 figures, 5 tables, submitted to AAS Journals. The full machine-readable tables and links to the catalog will be available after the acceptance of the pape

The OGLE collection of variable stars : nearly 66,000 Mira stars in the Milky Way

We present a collection of 65,981 Mira-type variable stars found in the Optical Gravitational Lensing Experiment (OGLE) project database. Two-thirds of our sample (40,356 objects) are located in the Galactic bulge fields, whereas 25,625 stars are in the Galactic disk. The vast majority of the collection (47,532 objects) comprises new discoveries. We provide basic observational parameters of the Mira variables: equatorial coordinates, pulsation periods, I-band and V-band mean magnitudes, I-band brightness amplitudes, and identifications in other catalogs of variable stars. We also provide the I-band and V-band time-series photometry collected since 1997 during the OGLE-II, OGLE-III, and OGLE-IV phases. The classical selection process, i.e., being mostly based on the visual inspection of light curves by experienced astronomers, has led to the high purity of the catalog. As a result, this collection can be used as a training set for machine-learning classification algorithms. Using overlapping areas of adjacent OGLE fields, we estimate the completeness of the catalog to be about 96%. We compare and discuss the statistical features of Miras located in different regions of the Milky Way. We show examples of stars that change their type over time, from a semiregular variable to Mira and vice versa. This data set is perfectly suited to studying the three-dimensional structure of the Milky Way, and it may help to explain the puzzle of the X-shaped bulge

A three-dimensional map of the milky way using 66,000 mira variable stars

We study the three-dimensional structure of the Milky Way using 65,981 Mira variable stars discovered by the Optical Gravitational Lensing Experiment survey. The spatial distribution of the Mira stars is analyzed with a model containing three barred components that include the X-shaped boxy component in the Galactic center (GC) and an axisymmetric disk. We take into account the distance uncertainties by implementing the Bayesian hierarchical inference method. The distance to the GC is R0 = 7.66 ± 0.01(stat.) ± 0.39(sys.) kpc, while the inclination of the major axis of the bulge to the Sun–GC line of sight is θ = 20fdg2 ± 0fdg6(stat.) ± 0fdg7(sys.). We present, for the first time, a detailed three-dimensional map of the Milky Way composed of young and intermediate-age stellar populations. Our analysis provides independent evidence for both the X-shaped bulge component and the flaring disk (being plausibly warped). We provide the complete data set of properties of Miras that were used for calculations in this work. The table includes mean brightness and amplitudes in nine photometric bands (covering a range of wavelengths from 0.5 to 12 μm), photometric chemical type, estimated extinction, and calculated distance with its uncertainty for each Mira variable. The median distance accuracy to a Mira star is at the level of 6.6%

Inhibition of neuroinflammation in BV2 microglia by the biflavonoid kolaviron is dependent on the Nrf2/ARE antioxidant protective mechanism

Kolaviron is a mixture of bioflavonoids found in the nut of the West African edible seed Garcinia kola, and it has been reported to exhibit a wide range of pharmacological activities. In this study, we investigated the effects of kolaviron in neuroinflammation. The effects of kolaviron on the expression of nitric oxide/inducible nitric oxide synthase (iNOS), prostaglandin E2 (PGE2)/cyclooxygenase-2, cellular reactive oxygen species (ROS) and the pro-inflammatory cytokines were examined in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. Molecular mechanisms of the effects of kolaviron on NF-B and Nrf2/ARE signalling pathways were analysed by immunoblotting, binding assay, and reporter assay. RNA interference was used to investigate the role of Nrf2 in the anti-inflammatory effect of kolaviron. Neuroprotective effect of kolaviron was assessed in a BV2 microglia/HT22 hippocampal neuron co-culture. Kolaviron inhibited the protein levels of NO/iNOS, PGE2/COX-2, cellular ROS and the proinflammatory cytokines (TNFα and IL-6) in LPS-stimulated microglia. Further mechanistic studies showed that kolaviron inhibited neuroinflammation by inhibiting IB/NF-B signalling pathway in LPS-activated BV2 microglia. Kolaviron produced antioxidant effect in BV2 microglia by increasing HO-1 via the Nrf2/ antioxidant response element (ARE) pathway. RNAi experiments revealed that Nrf2 is need for the anti-inflammatory effect of kolaviron. Kolaviron protected HT22 neurons from neuroinflammation-induced toxicity. Kolaviron inhibits neuroinflammation through Nrf2-dependent mechanisms. This compound may therefore be beneficial in neuroinflammation-related neurodegenerative disorders

Single-lens mass measurement in the high-magnification microlensing event Gaia 19bld located in the Galactic disc

CONTEXT: Microlensing provides a unique opportunity to detect non-luminous objects. In the rare cases that the Einstein radius θ_{E} and microlensing parallax π_{E} can be measured, it is possible to determine the mass of the lens. With technological advances in both ground- and space-based observatories, astrometric and interferometric measurements are becoming viable, which can lead to the more routine determination of θ_{E} and, if the microlensing parallax is also measured, the mass of the lens. AIMS: We present the photometric analysis of Gaia19bld, a high-magnification (A ≈ 60) microlensing event located in the southern Galactic plane, which exhibited finite source and microlensing parallax effects. Due to a prompt detection by the Gaia satellite and the very high brightness of I = 9.05 mag at the peak, it was possible to collect a complete and unique set of multi-channel follow-up observations, which allowed us to determine all parameters vital for the characterisation of the lens and the source in the microlensing event. METHODS: Gaia19bld was discovered by the Gaia satellite and was subsequently intensively followed up with a network of ground-based observatories and the Spitzer Space Telescope. We collected multiple high-resolution spectra with Very Large Telescope (VLT)/X-shooter to characterise the source star. The event was also observed with VLT Interferometer (VLTI)/PIONIER during the peak. Here we focus on the photometric observations and model the light curve composed of data from Gaia, Spitzer, and multiple optical, ground-based observatories. We find the best-fitting solution with parallax and finite source effects. We derived the limit on the luminosity of the lens based on the blended light model and spectroscopic distance. RESULTS: We compute the mass of the lens to be 1.13 ± 0.03 M_{⊙} and derive its distance to be 5.52_{−0.64}^{+0.35} kpc. The lens is likely a main sequence star, however its true nature has yet to be verified by future high-resolution observations. Our results are consistent with interferometric measurements of the angular Einstein radius, emphasising that interferometry can be a new channel for determining the masses of objects that would otherwise remain undetectable, including stellar-mass black holes

Up-regulation of human inducible nitric oxide synthase by p300 transcriptional complex

p300, a ubiquitous transcription coactivator, plays an important role in gene activation. Our previous work demonstrated that human inducible nitric oxide synthase (hiNOS) expression can be highly induced with the cytokine mixture (CM) of TNF-α + IL-1β + IFN-γ. In this study, we investigated the functional role of p300 in the regulation of hiNOS gene expression. Our initial data showed that overexpression of p300 significantly increased the basal and cytokine-induced hiNOS promoter activities in A549 cells. Interestingly, p300 activated cytokine-induced hiNOS transcriptional activity was completely abrogated by deleting the upstream hiNOS enhancer at -5 kb to -6 kb in the promoter. Furthermore, p300 over-expression increased cytokine-induced transcriptional activity on a heterologous minimal TK promoter with the same hiNOS enhancer. Site-directed mutagenesis of the hiNOS AP-1 motifs revealed that an intact upstream (-5.3kb) AP-1 binding site was critical for p300 mediated cytokine-induced hiNOS transcription. Furthermore, our ChIP analysis demonstrated that p300 was binding to Jun D and Fra-2 proteins at -5.3 kb AP-1 binding site in vivo. Lastly, our 3C assay was able to detect a long DNA loop between the hiNOS enhancer and core promoter site, and ChIP loop assay confirmed that p300 binds to AP-1 and RNA pol II proteins. Overall, our results suggest that coactivator p300 mediates cytokine-induced hiNOS transactivation by forming a distant DNA loop between its enhancer and core promoter region