Asbestos modulates thioredoxin-thioredoxin interacting protein interaction to regulate inflammasome activation

BACKGROUND: Asbestos exposure is related to various diseases including asbestosis and malignant mesothelioma (MM). Among the pathogenic mechanisms proposed by which asbestos can cause diseases involving epithelial and mesothelial cells, the most widely accepted one is the generation of reactive oxygen species and/or depletion of antioxidants like glutathione. It has also been demonstrated that asbestos can induce inflammation, perhaps due to activation of inflammasomes. METHODS: The oxidation state of thioredoxin was analyzed by redox Western blot analysis and ROS generation was assessed spectrophotometrically as a read-out of solubilized formazan produced by the reduction of nitrotetrazolium blue (NTB) by superoxide. Quantitative real time PCR was used to assess changes in gene transcription. RESULTS: Here we demonstrate that crocidolite asbestos fibers oxidize the pool of the antioxidant, Thioredoxin-1 (Trx1), which results in release of Thioredoxin Interacting Protein (TXNIP) and subsequent activation of inflammasomes in human mesothelial cells. Exposure to crocidolite asbestos resulted in the depletion of reduced Trx1 in human peritoneal mesothelial (LP9/hTERT) cells. Pretreatment with the antioxidant dehydroascorbic acid (a reactive oxygen species (ROS) scavenger) reduced the level of crocidolite asbestos-induced Trx1 oxidation as well as the depletion of reduced Trx1. Increasing Trx1 expression levels using a Trx1 over-expression vector, reduced the extent of Trx1 oxidation and generation of ROS by crocidolite asbestos, and increased cell survival. In addition, knockdown of TXNIP expression by siRNA attenuated crocidolite asbestos-induced activation of the inflammasome. CONCLUSION: Our novel findings suggest that extensive Trx1 oxidation and TXNIP dissociation may be one of the mechanisms by which crocidolite asbestos activates the inflammasome and helps in development of MM

Debris disks in main sequence binary systems

We observed 69 A3-F8 main sequence binary star systems using the Multiband Imaging Photometer for Spitzer onboard the Spitzer Space Telescope. We find emission significantly in excess of predicted photospheric flux levels for 9(+4/-3)% and 40(+7/-6)% of these systems at 24 and 70 microns, respectively. Twenty two systems total have excess emission, including four systems that show excess emission at both wavelengths. A very large fraction (nearly 60%) of observed binary systems with small (<3 AU) separations have excess thermal mission. We interpret the observed infrared excesses as thermal emission from dust produced by collisions in planetesimal belts. The incidence of debris disks around main sequence A3-F8 binaries is marginally higher than that for single old AFGK stars. Whatever combination of nature (birth conditions of binary systems) and nurture (interactions between the two stars) drives the evolution of debris disks in binary systems, it is clear that planetesimal formation is not inhibited to any great degree. We model these dust disks through fitting the spectral energy distributions and derive typical dust temperatures in the range 100--200 K and typical fractional luminosities around 10^-5, with both parameters similar to other Spitzer-discovered debris disks. Our calculated dust temperatures suggest that about half the excesses we observe are derived from circumbinary planetesimal belts and around one third of the excesses clearly suggest circumstellar material. Three systems with excesses have dust in dynamically unstable regions, and we discuss possible scenarios for the origin of this short-lived dust.Comment: ApJ, in press. 57 pages, including 7 figures (one of which is in color

Advantages and disadvantages of advertising and promotion in the internet

Nowadays, advertising plays an important role in the promotion and advancement of any brand, product or service. Advertising influences on the image and style of life. Internet is a tool which is used for creation of advertising. It represents an ideal opportunity for the development of communication with consumers in an electronic environment. Online advertising is used by companies worldwide for promotion their products and services. Features, advantages and disadvantages of the Internet - advertising will be covered in this article.На сегодняшний день, реклама играет важную роль в раскрутке и продвижении любого бренда, товара и услуги. Реклама оказывает влияние на образ и стиль жизни человека, диктует определенные модели поведения в обществе. Интернет - это инструмент, используемый при создании рекламы. Он представляет собой идеальную возможность для развития коммуникации с потребителями в электронной среде. Интернет-рекламу для продвижения своих товаров и услуг используют компании по всему миру. Особенности, преимущества и недостатки интернет - рекламы будут освещены в данной статье

Absorption-selected galaxies trace the low-mass, late-type, star-forming population at z∼2−3z\sim2-3

We report on the stellar content, half-light radii and star formation rates of a sample of 10 known high-redshift ($z\gtrsim 2$) galaxies selected on strong neutral hydrogen (HI) absorption (log(N(HI)/cm$^{-2})>19$) toward background quasars. We use observations from the {\it Hubble Space Telescope} (HST) Wide Field Camera 3 in three broad-band filters to study the spectral energy distribution(SED) of the galaxies. Using careful quasar point spread function subtraction, we study their galactic environments, and perform the first systematic morphological characterisation of such absorption-selected galaxies at high redshifts. Our analysis reveals complex, irregular hosts with multiple star-forming clumps. At a spatial sampling of 0.067 arcsec per pixel (corresponding to 0.55 kpc at the median redshift of our sample), 40% of our sample requires multiple S\'ersic components for an accurate modelling of the observed light distributions. Placed on the mass-size relation and the `main sequence' of star-forming galaxies, we find that absorption-selected galaxies at high redshift extend known relations determined from deep luminosity-selected surveys to an order of magnitude lower stellar mass, with objects primarily composed of star-forming, late-type galaxies. We measure half-light radii in the range $r_{1/2} \sim$ 0.4 to 2.6 kpc based on the reddest band (F160W) to trace the oldest stellar populations, and stellar masses in the range $\log (\mathrm{M}_{\star}/\mathrm{M}_{\odot}) \sim$ 8 to 10 derived from fits to the broad-band SED. Spectroscopic and SED-based star formation rates are broadly consistent, and lie in the range log(SFR/M$_{\odot}$yr$^{-1}$) $\sim$0.0 to 1.7.Comment: 17 pages, Accepted for publication in MNRAS. This revision has minor text change

Constraints on a Massive Dirac Neutrino Model

We examine constraints on a simple neutrino model in which there are three massless and three massive Dirac neutrinos and in which the left handed neutrinos are linear combinations of doublet and singlet neutrinos. We examine constraints from direct decays into heavy neutrinos, indirect effects on electroweak parameters, and flavor changing processes. We combine these constraints to examine the allowed mass range for the heavy neutrinos of each of the three generations.Comment: latex, 29 pages, 7 figures (not included), MIT-CTP-221

Closed-flavor pi + J/psi and pi + Upsilon Cross Sections at Low Energies from Dipion Decays

The scale of low energy c-cbar and b-bbar cross sections on light hadrons is of great importance to searches for the quark gluon plasma using the heavy-quarkonium suppression signature. Unfortunately, little is known about these near-threshold cross sections at present, and recent theoretical estimates span many orders of magnitude. Here we use experimental data on the four observed closed-flavor heavy quarkonium hadronic decays psi' -> pi pi J/psi, Upsilon' -> pi pi Upsilon, Upsilon'' -> pi pi Upsilon and Upsilon'' -> pi pi Upsilon', combined with simple models of the transition amplitudes, to estimate the pion scattering cross sections of c-cbar and b-bbar mesons near threshold. Specifically we consider the closed-flavor reactions pi J/psi -> pi psi', pi Upsilon -> pi Upsilon', pi Upsilon -> pi Upsilon'' and pi Upsilon' -> pi Upsilon'' and their time-reversed analogues. Our results may be useful in constraining theoretical models of the strong interactions of heavy quarkonia, and can be systematically improved through future detailed studies of dipion decays, notably psi' -> pi pi J/psi and Upsilon'' -> pi pi Upsilon.Comment: 6 pages, 6 figure

Synthesis, Characterization and Magnetic Susceptibility of the Heavy Fermion Transition Metal Oxide LiV_{2}O_{4}

The preparative method, characterization and magnetic susceptibility \chi measurements versus temperature T of the heavy fermion transition metal oxide LiV_{2}O_{4} are reported in detail. The intrinsic \chi(T) shows a nearly T-independent behavior below ~ 30 K with a shallow broad maximum at about 16 K, whereas Curie-Weiss-like behavior is observed above 50-100 K. Field-cooled and zero-field-cooled magnetization M measurements in applied magnetic fields H = 10 to 100 G from 1.8 to 50 K showed no evidence for spin-glass ordering. Crystalline electric field theory for an assumed cubic V point group symmetry is found insufficient to describe the observed temperature variation of the effective magnetic moment. The Kondo and Coqblin-Schrieffer models do not describe the magnitude and T dependence of \chi with realistic parameters. In the high T range, fits of \chi(T) by the predictions of high temperature series expansion calculations provide estimates of the V-V antiferromagnetic exchange coupling constant J/k_{B} ~ 20 K, g-factor g ~ 2 and the T-independent susceptibility. Other possible models to describe the \chi(T) are discussed. The paramagnetic impurities in the samples were characterized using isothermal M(H) measurements with 0 < H <= 5.5 Tesla at 2 to 6 K. These impurities are inferred to have spin S_{imp} ~ 3/2 to 4, g_{imp} ~ 2 and molar concentrations of 0.01 to 0.8 %, depending on the sample.Comment: 19 typeset RevTeX pages, 16 eps figures included, uses epsf; to be published in Phys. Rev.

Angular Momentum and the Formation of Stars and Black Holes

The formation of compact objects like stars and black holes is strongly constrained by the requirement that nearly all of the initial angular momentum of the diffuse material from which they form must be removed or redistributed during the formation process. The mechanisms that may be involved and their implications are discussed for (1) low-mass stars, most of which probably form in binary or multiple systems; (2) massive stars, which typically form in clusters; and (3) supermassive black holes that form in galactic nuclei. It is suggested that in all cases, gravitational interactions with other stars or mass concentrations in a forming system play an important role in redistributing angular momentum and thereby enabling the formation of a compact object. If this is true, the formation of stars and black holes must be a more complex, dynamic, and chaotic process than in standard models. The gravitational interactions that redistribute angular momentum tend to couple the mass of a forming object to the mass of the system, and this may have important implications for mass ratios in binaries, the upper stellar IMF in clusters, and the masses of supermassive black holes in galaxies.Comment: Accepted by Reports on Progress in Physic

Chandra spectroscopy of the hot star beta Crucis and the discovery of a pre-main-sequence companion

In order to test the O star wind-shock scenario for X-ray production in less luminous stars with weaker winds, we made a pointed 74 ks observation of the nearby early B giant, beta Cru (B0.5 III), with the Chandra HETGS. We find that the X-ray spectrum is quite soft, with a dominant thermal component near 3 million K, and that the emission lines are resolved but quite narrow, with half-widths of 150 km/s. The forbidden-to-intercombination line ratios of Ne IX and Mg XI indicate that the hot plasma is distributed in the wind, rather than confined near the photosphere. It is difficult to understand the X-ray data in the context of the standard wind-shock paradigm for OB stars, primarily because of the narrow lines, but also because of the high X-ray production efficiency. A scenario in which the bulk of the outer wind is shock heated is broadly consistent with the data, but not very well motivated theoretically. It is possible that magnetic channeling could explain the X-ray properties, although no field has been detected on beta Cru. We detected periodic variability in the hard (hnu > 1 keV) X-rays, modulated on the known optical period of 4.58 hours, which is the period of the primary beta Cep pulsation mode for this star. We also have detected, for the first time, an apparent companion to beta Cru at a projected separation of 4 arcsec. This companion was likely never seen in optical images because of the presumed very high contrast between it and beta Cru in the optical. However, the brightness contrast in the X-ray is only 3:1, which is consistent with the companion being an X-ray active low-mass pre-main-sequence star. The companion's X-ray spectrum is relatively hard and variable, as would be expected from a post T Tauri star.Comment: Accepted for publication in MNRAS; 19 pages, 15 figures, some in color; version with higher-resolution figures available at http://astro.swarthmore.edu/~cohen/papers/bcru_mnras2008.pd