The baryon density at z=0.9-1.9 - Tracing the warm-hot intergalactic medium with broad Lyman alpha absorption

We present an analysis of the Lyman alpha forests of five quasar spectra in the near UV. Properties of the intergalactic medium (IGM) at an intermediate redshift interval (0.9 < z < 1.9) are studied. The amount of baryons in the diffuse photoionised IGM and the warm-hot intergalactic medium (WHIM) are traced to get constraints on the redshift evolution of the different phases of the intergalactic gas. The baryon density of the diffuse IGM is determined with photoionisation calculations under the assumption of local hydrostatic equilibrium. We assume that the gas is ionised by a metagalactic background radiation with a Haardt & Madau (2001) spectrum. The WHIM is traced with broad Lyman alpha (BLA) absorption. The properties of a number of BLA detections are studied. Under the assumption of collisional ionisation equilibrium a lower limit to the baryon density could be estimated. It is found that the diffuse photoionised IGM contains at least 25% of the total baryonic matter at redshifts 1 < z < 2. For the WHIM a lower limit of 2.4% could be determined. Furthermore the data indicates that the intergalactic gas is in a state of evolution at z=1.5. We confirm that a considerable part of the WHIM is created between z=1 and z=2.Comment: 6 pages, 1 figure, accepted for publication in A&

The Evolution of Lyman alpha Absorbers in the Redshift Range 0.5<z<1.9

We investigate the evolution and the statistical properties of the Lya absorbers of the intergalactic medium (IGM) in the largely unexplored redshift range z=0.5-1.9. We use high-resolution (R > 30,000) UV (STIS) and optical (VLT/UVES and Keck/HIRES) spectra of nine bright quasars with z_em < 1.94. The main results for the combined Lya line sample are summarized as follows: 1. The evolution of the number density of the absorbers can be described by the power law dn/dz ~ (1+z)^gamma. The number density of the low column density lines decreases with decreasing z with gamma=0.74+-0.31 in the interval z=0.7-1.9. A comparison with results at higher redshifts shows that it is decelerated in the explored redshift range and turns into a flat evolution for z -> 0. The stronger absorbers thin out faster (gamma=1.50+-0.45). The break in their evolution predicted for z=1.5-1.7 cannot be seen down to z=0.7. On the other hand, a comparison with values from the literature for the local number density gives a hint that this break occurs at lower redshift. 2. The distribution of the column densities of the absorbers is complete down to N_HI=10^12.90 cm^-2. It can be approximated by a single power law with the exponent beta=1.60+-0.03 over almost three orders of magnitude. beta is redshift independent. 3. The Lya lines with lower column densities as well as the higher column density lines show marginal clustering with a 2 sigma significance over short distances (Delta v < 200 km/s and Delta v < 100 km/s, respectively). We do not see any difference in the clustering with either column density or redshift.Comment: 15 pages, 18 figures, accepted for publication in Astronomy & Astrophysic

HE 0141-3932: a bright QSO with an unusual emission line spectrum and associated absorption

HE 0141-3932 (zem = 1.80) is a bright blue radio-quite quasar with an unusually weak Ly-alpha emission line. Large redshift differences (Delta z = 0.05) are observed between high ionization and low ionization emission lines. Absorption systems identified at zabs = 1.78, 1.71, and 1.68 show mild oversolar metallicities (Z ~= 1-2Zsolar) and can be attributed to the associated gas clouds ejected from the circumnuclear region. The joint analysis of the emission and absorption lines leads to the conclusion that this quasar is seen almost pole-on. Its apparent luminosity may be Doppler boosted by ~10 times. The absorbing gas shows a high abundance of Fe, Mg and Al ([Fe, Mg, Al/C] ~= 0.15 +/- 0.10) along with underabundance of N ([N/C] <= -0.5). This abundance pattern is at variance with current chemical evolution models of QSOs predicting [N/C] >= 0$ and [Fe/C] < 0 at Z ~ Zsolar.Comment: 12 pages, 6 figures, accepted for publication in A&

Nitrogen-deficient and iron-rich associated absorbers with oversolar metallicities towards the quasar HE0141-3932

HE0141-3932 (zem=1.80) is a bright blue radio-quite quasar which reveals an emission line spectrum with an unusually weak Ly-alpha line. In addition, large redshift differences (Delta z=0.05) are observed between high ionization and low ionization emission lines. Absorption systems identified at z=1.78, 1.71, and 1.68 show mild oversolar metallicities (Z ~= 1-2Zsolar) and can be attributed to the associated gas clouds ejected from the circumnuclear region. The joint analysis of the emission and absorption lines leads to the conclusion that this quasar is seen almost pole-on. Its apparent luminosity may be Doppler boosted by ~10 times. The absorbing gas shows high abundance of Fe, Mg, and Al ([Fe, Mg, Al/C] ~= 0.15+/-0.10) along with underabundance of N ([N/C]<=-0.5). This abundance pattern is at variance with current chemical evolution models of QSOs predicting [N/C]>0 and [Fe/C]<0 at Z ~ Zsolar. Full details of this work are given in Reimers et al. (2005).Comment: 2 pages, to appear in the Proceed. of IAU Symp.228 "From Lithium to Uranium: Elemental Tracers of Early Cosmic Evolution", eds. V.Hill, P.Francois and F.Prima

Fv antibodies to aflatoxin B1 derived from a pre-immunized antibody phage display library system

The production and characterization of recombinant antibodies to aflatoxin B[SUB1] (AFB[SUB1]), a potent mycotoxin and carcinogen is described. The antibody fragments produced were then applied for use in a surface plasmon resonance-based biosensor (BIAcore), which measures biomolecular interactions in 'real-time'. Single chain Fv (scFv) antibodies were generated to aflatoxin B1 from an established phage display system, which incorporated a range of different plasmids for efficient scFv expression. The scFv's were used in the development of a competitive ELISA, and also for the development of surface plasmon resonance (SPR)-based inhibition immunoassays. They were found to be suitable for the detection of AFB[SUB1], in this format, with the assays being sensitive and reproducible

Molecular dynamics simulations and in silico peptide ligand screening of the Elk-1 ETS domain

Background: The Elk-1 transcription factor is a member of a group of proteins called ternary complex factors, which serve as a paradigm for gene regulation in response to extracellular signals. Its deregulation has been linked to multiple human diseases including the development of tumours. The work herein aims to inform the design of potential peptidomimetic compounds that can inhibit the formation of the Elk-1 dimer, which is key to Elk-1 stability. We have conducted molecular dynamics simulations of the Elk-1 ETS domain followed by virtual screening. Results: We show the ETS dimerisation site undergoes conformational reorganisation at the a1b1 loop. Through exhaustive screening of di- and tri-peptide libraries against a collection of ETS domain conformations representing the dynamics of the loop, we identified a series of potential binders for the Elk-1 dimer interface. The di-peptides showed no particular preference toward the binding site; however, the tri-peptides made specific interactions with residues: Glu17, Gln18 and Arg49 that are pivotal to the dimer interface. Conclusions: We have shown molecular dynamics simulations can be combined with virtual peptide screening to obtain an exhaustive docking protocol that incorporates dynamic fluctuations in a receptor. Based on our findings, we suggest experimental binding studies to be performed on the 12 SILE ranked tri-peptides as possible compounds for the design of inhibitors of Elk-1 dimerisation. It would also be reasonable to consider the score ranked tri-peptides as a comparative test to establish whether peptide size is a determinant factor of binding to the ETS domain

Prostate-Specific Ets (PSE) factor: a novel marker for detection of metastatic breast cancer in axillary lymph nodes

Prostate Specific Ets factor is a recently identified transcriptional activator that is overexpressed in prostate cancer. To determine whether this gene is overexpressed in breast cancer, we performed a virtual Northern blot using data available online at the Cancer Genome Anatomy Project website. Ninety-five SAGE libraries were probed with a unique sequence tag to the Prostate Specific Ets gene. The results indicate that Prostate Specific Ets is expressed in 14 out of 15 breast cancer libraries (93%), nine out of 10 prostate cancer libraries (90%), three out of 40 libraries from other cancers (7.5%), and four out of 30 normal tissue libraries (13%). To determine the possibility that the Prostate Specific Ets gene is a novel marker for detection of metastatic breast cancer in axillary lymph nodes, quantitative real-time RT–PCR analyses were performed. The mean level of Prostate Specific Ets expression in lymph nodes containing metastatic breast cancer (n=22) was 410-fold higher than in normal lymph node (n=51). A receiver operator characteristic curve analysis indicated that Prostate Specific Ets was overexpressed in 18 out of 22 lymph nodes containing metastatic breast cancer (82%). The receiver operator characteristic curve analysis also indicated that the diagnostic accuracy of the Prostate Specific Ets gene for detection of metastatic breast cancer in axillary lymph nodes was 0.949. These results provide evidence that Prostate Specific Ets is a potentially informative novel marker for detection of metastatic breast cancer in axillary lymph nodes, and should be included in any study that involves molecular profiling of breast cancer

Alternative splicing and nonsense-mediated decay regulate telomerase reverse transcriptase (TERT) expression during virus-induced lymphomagenesis in vivo

<p>Abstract</p> <p>Background</p> <p>Telomerase activation, a critical step in cell immortalization and oncogenesis, is partly regulated by alternative splicing. In this study, we aimed to use the Marek's disease virus (MDV) T-cell lymphoma model to evaluate TERT regulation by splicing during lymphomagenesis <it>in vivo</it>, from the start point to tumor establishment.</p> <p>Results</p> <p>We first screened cDNA libraries from the chicken MDV lymphoma-derived MSB-1 T- cell line, which we compared with B (DT40) and hepatocyte (LMH) cell lines. The chTERT splicing pattern was cell line-specific, despite similar high levels of telomerase activity. We identified 27 alternative transcripts of chicken TERT (chTERT). Five were in-frame alternative transcripts without <it>in vitro </it>telomerase activity in the presence of viral or chicken telomerase RNA (vTR or chTR), unlike the full-length transcript. Nineteen of the 22 transcripts with a premature termination codon (PTC) harbored a PTC more than 50 nucleotides upstream from the 3' splice junction, and were therefore predicted targets for nonsense-mediated decay (NMD). The major PTC-containing alternatively spliced form identified in MSB1 (ie10) was targeted to the NMD pathway, as demonstrated by UPF1 silencing. We then studied three splicing events separately, and the balance between in-frame alternative splice variants (d5f and d10f) plus the NMD target i10ec and constitutively spliced chTERT transcripts during lymphomagenesis induced by MDV indicated that basal telomerase activity in normal T cells was associated with a high proportion of in-frame non functional isoforms and a low proportion of constitutively spliced chTERT. Telomerase upregulation depended on an increase in active constitutively spliced chTERT levels and coincided with a switch in alternative splicing from an in-frame variant to NMD-targeted variants.</p> <p>Conclusions</p> <p>TERT regulation by splicing plays a key role in telomerase upregulation during lymphomagenesis, through the sophisticated control of constitutive and alternative splicing. Using the MDV T-cell lymphoma model, we identified a chTERT splice variant as a new NMD target.</p

p68/DdX5 supports β-Catenin &amp; RNAP II during androgen receptor mediated transcription in prostate cancer

The DEAD box RNA helicase p68 (Ddx5) is an important androgen receptor (AR) transcriptional co-activator in prostate cancer (PCa) and is over-expressed in late stage disease. β-Catenin is a multifunctional protein with important structural and signalling functions which is up-regulated in PCa and similar to p68, interacts with the AR to co-activate expression of AR target genes. Importantly, p68 forms complexes with nuclear β-Catenin and promotes gene transcription in colon cancer indicating a functional interplay between these two proteins in cancer progression. In this study, we explore the relationship of p68 and β-Catenin in PCa to assess their potential co-operation in AR-dependent gene expression, which may be of importance in the development of castrate resistant prostate cancer (CRPCa). We use immunoprecipitation to demonstrate a novel interaction between p68 and β-Catenin in the nucleus of PCa cells, which is androgen dependent in LNCaP cells but androgen independent in a hormone refractory derivative of the same cell line (representative of the CRPCa disease type). Enhanced AR activity is seen in androgen-dependent luciferase reporter assays upon transient co-transfection of p68 and β-Catenin as an additive effect, and p68-depleted Chromatin-Immunoprecipitation (ChIP) showed a decrease in the recruitment of the AR and β-Catenin to androgen responsive promoter regions. In addition, we found p68 immunoprecipitated with the processive and non-processive form of RNA polymerase II (RNAP II) and show p68 recruited to elongating regions of the AR mediated PSA gene, suggesting a role for p68 in facilitating RNAP II transcription of AR mediated genes. These results suggest p68 is important in facilitating β-Catenin and AR transcriptional activity in PCa cells