The Role of RNA Polymerase II Elongation Control in HIV-1 Gene Expression, Replication, and Latency

HIV-1 usurps the RNA polymerase II elongation control machinery to regulate the expression of its genome during lytic and latent viral stages. After integration into the host genome, the HIV promoter within the long terminal repeat (LTR) is subject to potent downregulation in a postinitiation step of transcription. Once produced, the viral protein Tat commandeers the positive transcription elongation factor, P-TEFb, and brings it to the engaged RNA polymerase II (Pol II), leading to the production of viral proteins and genomic RNA. HIV can also enter a latent phase during which factors that regulate Pol II elongation may play a role in keeping the virus silent. HIV, the causative agent of AIDS, is a worldwide health concern. It is hoped that knowledge of the mechanisms regulating the expression of the HIV genome will lead to treatments and ultimately a cure

Anisotropy of the space orientation of radio sources. I: The catalog

A catalog of the extended extragalactic radio sources consisting of 10461 objects is compiled based on the list of radio sources of the FIRST survey. A total of 1801 objects are identified with galaxies and quasars of the SDSS survey and the Veron-Veron catalog. The distribution of the position angles of the axes of radio sources from the catalog is determined, and the probability that this distribution is equiprobable is shown to be less then 10^(-7). This result implies that at Z equal to or smaller then 0.5, spatial orientation of the axes of radio sources is anisotropic at a statistically significant level.Comment: 8 pages, 7 figure

On the Relation Between Peak Luminosity and Parent Population of Type Ia Supernovae: A New Tool for Probing the Ages of Distant Galaxies

We study the properties of Type Ia Supernovae (SNe Ia) as functions of the radial distance from their host galaxy centers. Using a sample of 62 SNe Ia with reliable luminosity, reddening, and decline rate determinations, we find no significant radial gradients of SNe Ia peak absolute magnitudes or decline rates in elliptical+S0 galaxies, suggesting that the diversity of SN properties is not related to the metallicity of their progenitors. We do find that the range in brightness and light curve width of supernovae in spiral galaxies extends to brighter, broader values. These results are interpreted as support for an age, but not metallicity, related origin of the diversity in SNe Ia. If confirmed with a larger and more accurate sample of data, the age-luminosity relation would offer a new and powerful tool to probe the ages and age gradients of stellar populations in galaxies at redshift as high as $z\sim1-2$. The absence of significant radial gradients in the peak $\rm (B-V)_0$ and $\rm (V-I)_0$ colors of SNe Ia supports the redding correction method of Phillips et al (1999). We find no radial gradient in residuals from the SN Ia luminosity-width relation, suggesting that the relation is not affected by properties of the progenitor populations and supporting the reliability of cosmological results based upon the use of SNe Ia as distance indicators.Comment: 19 pages, incl. 3 tables & 3 figures; to appear in Nov 2000 issue of Ap

Fracture Propagation Driven by Fluid Outflow from a Low-permeability Aquifer

Deep saline aquifers are promising geological reservoirs for CO2 sequestration if they do not leak. The absence of leakage is provided by the caprock integrity. However, CO2 injection operations may change the geomechanical stresses and cause fracturing of the caprock. We present a model for the propagation of a fracture in the caprock driven by the outflow of fluid from a low-permeability aquifer. We show that to describe the fracture propagation, it is necessary to solve the pressure diffusion problem in the aquifer. We solve the problem numerically for the two-dimensional domain and show that, after a relatively short time, the solution is close to that of one-dimensional problem, which can be solved analytically. We use the relations derived in the hydraulic fracture literature to relate the the width of the fracture to its length and the flux into it, which allows us to obtain an analytical expression for the fracture length as a function of time. Using these results we predict the propagation of a hypothetical fracture at the In Salah CO2 injection site to be as fast as a typical hydraulic fracture. We also show that the hydrostatic and geostatic effects cause the increase of the driving force for the fracture propagation and, therefore, our solution serves as an estimate from below. Numerical estimates show that if a fracture appears, it is likely that it will become a pathway for CO2 leakage.Comment: 21 page

Sequence specificity incompletely defines the genome-wide occupancy of Myc

BACKGROUND: The Myc-Max heterodimer is a transcription factor that regulates expression of a large number of genes. Genome occupancy of Myc-Max is thought to be driven by Enhancer box (E-box) DNA elements, CACGTG or variants, to which the heterodimer binds in vitro. RESULTS: By analyzing ChIP-Seq datasets, we demonstrate that the positions occupied by Myc-Max across the human genome correlate with the RNA polymerase II, Pol II, transcription machinery significantly better than with E-boxes. Metagene analyses show that in promoter regions, Myc is uniformly positioned about 100 bp upstream of essentially all promoter proximal paused polymerases with Max about 15 bp upstream of Myc. We re-evaluate the DNA binding properties of full length Myc-Max proteins. Electrophoretic mobility shift assay results demonstrate Myc-Max heterodimers display significant sequence preference, but have high affinity for any DNA. Quantification of the relative affinities of Myc-Max for all possible 8-mers using universal protein-binding microarray assays shows that sequences surrounding core 6-mers significantly affect binding. Compared to the in vitro sequence preferences, Myc-Max genomic occupancy measured by ChIP-Seq is largely, although not completely, independent of sequence specificity. CONCLUSIONS: We quantified the affinity of Myc-Max to all possible 8-mers and compared this with the sites of Myc binding across the human genome. Our results indicate that the genomic occupancy of Myc cannot be explained by its intrinsic DNA specificity and suggest that the transcription machinery and associated promoter accessibility play a predominant role in Myc recruitment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-014-0482-3) contains supplementary material, which is available to authorized users

Lifting the Veil of Dust from NGC 0959: The Importance of a Pixel-Based 2D Extinction Correction

We present the results of a study of the late-type spiral galaxy NGC 0959, before and after application of the pixel-based dust extinction correction described in Tamura et al. 2009 (Paper I). Galaxy Evolution Explorer (GALEX) far-UV (FUV) and near-UV (NUV), ground-based Vatican Advanced Technology Telescope (VATT) UBVR, and Spitzer/Infrared Array Camera (IRAC) 3.6, 4.5, 5.8, and 8.0 micron images are studied through pixel Color-Magnitude Diagrams (pCMDs) and pixel Color-Color Diagrams (pCCDs). We define groups of pixels based on their distribution in a pCCD of (B - 3.6 micron) versus (FUV - U) colors after extinction correction. In the same pCCD, we trace their locations before the extinction correction was applied. This shows that selecting pixel groups is not meaningful when using colors uncorrected for dust. We also trace the distribution of the pixel groups on a pixel coordinate map of the galaxy. We find that the pixel-based (two-dimensional) extinction correction is crucial to reveal the spatial variations in the dominant stellar population, averaged over each resolution element. Different types and mixtures of stellar populations, and galaxy structures such as a previously unrecognized bar, become readily discernible in the extinction-corrected pCCD and as coherent spatial structures in the pixel coordinate map.Comment: 10 pages, LaTeX2e requires 'emulateapj.cls', 'graphicx.sty', and 'natbib.sty' (included), 9 postscript figures, 1 table. Accepted for publication in AJ

Structure of Disk Dominated Galaxies I. Bulge/Disk Parameters, Simulations, and Secular Evolution

(Abridged) A robust analysis of galaxy structural parameters, based on the modeling of bulge and disk brightnesses in the BVRH bandpasses, is presented for 121 face-on and moderately inclined late-type spirals. Each surface brightness (SB) profile is decomposed into a sum of a generalized Sersic bulge and an exponential disk. The reliability and limitations of our bulge-to-disk (B/D) decompositions are tested with extensive simulations of galaxy brightness profiles (1D) and images (2D). Galaxy types are divided into 3 classes according to their SB profile shapes; Freeman Type-I and Type-II, and a third ``Transition'' class for galaxies whose profiles change from Type-II in the optical to Type-I in the infrared. We discuss possible interpretations of Freeman Type-II profiles. The Sersic bulge shape parameter for nearby Type-I late-type spirals shows a range between n=0.1-2 but, on average, the underlying surface density profile for the bulge and disk of these galaxies is adequately described by a double-exponential distribution. We confirm a coupling between the bulge and disk with a scale length ratio r_e/h=0.22+/-0.09, or h_bulge/h_disk=0.13+/-0.06 for late-type spirals, in agreement with recent N-body simulations of disk formation and models of secular evolution. This ratio increases from ~0.20 for late-type spirals to ~0.24 for earlier types. The similar scaling relations for early and late-type spirals suggest comparable formation and/or evolution scenarios for disk galaxies of all Hubble types.Comment: 78 pages with 23 embedded color figures + tables of galaxy structural parameters. Accepted for publication in the Astrophysical Journal. The interested reader is strongly encouraged to ignore some of the low res figures within; instead, download the high resolution version from http://www.astro.ubc.ca/people/courteau/public/macarthur02_disks.ps.g

Potential Diagnostic Assay for Cystinuria by Capillary Electrophoresis Coupled to Mass Spectrometry

Cistinúria é uma alteração genética autossômica recessiva caracterizada por transporte intestinal e renal anormal tubular de L-cistina, assim como de L-lisina, L-arginina e L-ornitina. Esta alteração leva a excreção urinária excessiva destes aminoácidos com a formação de pedras nos rins provocados pela baixa solubilidade de L-cistina na urina. Neste trabalho, um método analítico para a determinação destes quatro aminoácidos por eletroforese capilar acoplada à espectrometria de massas com ionização por electrospray (CE-ESI-MS) foi desenvolvido e validado. Usando soluções padrão de L-cistina, L-lisina, L-arginina e L-ornitina, os limites de detecção dos aminoácidos por este método foram 114,2, 61,3, 72,7 e 86,7 µmol L -1 . Soluções padrão foram amostrados em um capilar de sílica (50 µm de diâmetro interno e 70 cm de comprimento total) e injeção de 2 psi de pressão por 10 s. A separação ocorreu a 300 V cm -1 , utilizando 1,0 mol L -1 de ácido fórmico em 10% de metanol em água como eletrólito de separação. Aplicação do método para a urina de um paciente diagnosticado clinicamente como portador de cistinúria revelou a presença de 900,5 ± 5, 600,0 ± 2, 700,2 ± 1 e 500,0 ± 3 µmol L -1 de aminoácidos, respectivamente, e 75,3 ± 1 µmol L -1 de creatinina. O método de CE-ESI-MS descrito neste trabalho para a análise de L-cistina e outros aminoácidos associados com cistinúria constitui uma ferramenta para diagnóstico sensível e confiável para caracterização e monitoramento desta doença. Cystinuria is an autosomal recessive genetic disorder characterized by abnormal intestinal and renal tubular transport of L-cystine as well as of L-lysine, L-arginine and L-ornithine. This leads to excessive urinary excretion of amino acids, with the formation of kidney stones caused by the low solubility of L-cystine in the urine. In this study, an analytical method for simultaneous determination of these four amino acids in urine by capillary electrophoresis coupled to electrospray ionization mass spectrometry (CE-ESI-MS) was developed and validated. Using standard solutions of L-cystine, L-lysine, L-arginine and L-ornithine, the amino acid detection limits by this method were 114.2, 61.3, 72.7 and 86.7 µmol L -1 . Standard solutions were injected in a silica capillary column (50 mm i.d. and 70 cm length) under 2 psi of pressure by 10 s. The separation occurred at 300 V cm -1 , using 1.0 mol L -1 formic acid in 10% methanol in water as the background electrolyte. The method was applied to the urine of a patient clinically diagnosed as a cystinuria carrier, which revealed the presence of 900.5 ± 5, 600.0 ± 2, 700.2 ± 1 and 500.0 ± 3 µmol L -1 of amino acid, respectively, and 75.3 ± 1 µmol L -1 of creatinine. The CE-ESI-MS method described here for analyzing L-cystine and other cystinuria-related amino acids is a sensitive and reliable diagnostic tool for characterizing and monitoring this disease. Keywords: cystinuria, CE/ESI-MS, inborn error of metabolism, clinical analysis Barbosa et al

Influence of Gamma-Ray Emission on the Isotopic Composition of Clouds in the Interstellar Medium

We investigate one mechanism of the change in the isotopic composition of cosmologically distant clouds of interstellar gas whose matter was subjected only slightly to star formation processes. According to the standard cosmological model, the isotopic composition of the gas in such clouds was formed at the epoch of Big Bang nucleosynthesis and is determined only by the baryon density in the Universe. The dispersion in the available cloud composition observations exceeds the errors of individual measurements. This may indicate that there are mechanisms of the change in the composition of matter in the Universe after the completion of Big Bang nucleosynthesis. We have calculated the destruction and production rates of light isotopes (D, 3He, 4He) under the influence of photonuclear reactions triggered by the gamma-ray emission from active galactic nuclei (AGNs). We investigate the destruction and production of light elements depending on the spectral characteristics of the gamma-ray emission. We show that in comparison with previous works, taking into account the influence of spectral hardness on the photonuclear reaction rates can increase the characteristic radii of influence of the gamma-ray emission from AGNs by a factor of 2-8. The high gamma-ray luminosities of AGNs observed in recent years increase the previous estimates of the characteristic radii by two orders of magnitude. This may suggest that the influence of the emission from AGNs on the change in the composition of the medium in the immediate neighborhood (the host galaxy) has been underestimated.Comment: 13 pages, 13 figures, 3 table