High-resolution X-ray spectroscopy of the low and high states of the Seyfert 1 galaxy NGC 4051 with Chandra LETGS

Methods. We analyse two observations taken with the Low Energy Transmission Grating Spectrometer of Chandra. We investigated the spectral response to a sudden flux decrease by a factor of 5, which occurred during the second observation. Results. We detect a highly ionised absorption component with an outflow velocity of -4670 km/s, one of the highest outflow velocity components observed in a Seyfert 1 galaxy. The spectra contain a relativistic O VIII Ly alpha line, and four absorption components spanning a range in ionisation parameter xi between 0.07 and 3.19. An emission component producing radiative recombination continua of C VI and C V appears during the low state. The black body temperature decreases with the drop in flux observed in the second observation. Conclusions. For all absorber components we exclude that the ionisation parameter linearly responded to the decrease in flux by a factor of 5. The variability of the absorber suggest that at least three out of four detected components are located in the range 0.02-1 pc. ABRIDGEDComment: Accepted by A&A, 14 pages, 9 figure

Variations in activin receptor, inhibin/activin subunit and follistatin mRNAs in human prostate tumour tissues

The possible role of activin in the regulation of malignant prostatic growth was studied using RNAase protection assays of activin receptors, inhibin/activin subunits and follistatin mRNAs in the human prostatic carcinoma cell lines LNCaP-FGC, -R and -LNO, in human prostatic carcinoma xenografts and in human prostatic tissue. Activin receptor types IA (ActRIA), IB (ActRIB), IIA (ActRIIA) and IIB (ActRIIB) mRNAs were generally expressed in prostate pithelial cells, with significantly lower levels of ActRIB mRNA in prostate tumour aterial when compared to non-malignant tissue (P< 0.05; Mann–Whitney U -test). Inhibin/activin βA- and βB-subunit mRNA expression was also found in prostate tissue. Androgen-independent xenografts expressed significantly lower amounts of βB-subunit mRNA when compared to androgen-dependent xenografts (P< 0.05). While βB-subunit mRNA was expressed by LNCaP-FGC and -LNO cells, virtually no expression was found in the androgen-independent LNCaP-R line. Inhibin α-subunit mRNA levels were low or undetectable in all samples investigated. Follistatin mRNA was undetectable in LNCaP-sublines, while low levels were found in prostatic tissues. In androgen-independent LNCaP-R cells, activin inhibited cell growth in a dose-dependent manner. These results suggest that prostate tumour progression is accompanied by a decrease of the inhibitory effect of locally produced activin by either a decrease in the expression of activin βB-subunit mRNA or by a decrease of ActRIB mRNA levels. © 2000 Cancer Research Campaig

Simultaneous X-ray and UV spectroscopy of the Seyfert 1 galaxy NGC 5548.II. Physical conditions in the X-ray absorber

We present the results from a 500 ks Chandra observation of the Seyfert 1 galaxy NGC 5548. We detect broadened emission lines of O VII and C VI in the spectra, similar to those observed in the optical and UV bands. The source was continuously variable, with a 30 % increase in luminosity in the second half of the observation. No variability in the warm absorber was detected between the spectra from the first 170 ks and the second part of the observation. The velocity structure of the X-ray absorber is consistent with the velocity structure measured simultaneously in the ultraviolet spectra. We find that the highest velocity outflow component, at -1040 km/s, becomes increasingly important for higher ionization parameters. This velocity component spans at least three orders of magnitude in ionization parameter, producing both highly ionized X-ray absorption lines (Mg XII, Si XIV) as well as UV absorption lines. A similar conclusion is very probable for the other four velocity components. Based upon our observations, we argue that the warm absorber probably does not manifest itself in the form of photoionized clumps in pressure equilibrium with a surrounding wind. Instead, a model with a continuous distribution of column density versus ionization parameter gives an excellent fit to our data. From the shape of this distribution and the assumption that the mass loss through the wind should be smaller than the accretion rate onto the black hole, we derive upper limits to the solid angle as small as 10^{-4} sr. From this we argue that the outflow occurs in density-stratified streamers. The density stratification across the stream then produces the wide range of ionization parameter observed in this source. Abridged.Comment: 21 pages, 12 figures accepted for publication in A&

Characterization of a zinc-finger protein and its association with apoptosis in prostate cancer cells

BACKGROUND: The transition from androgen-dependent to androgen-independent prostate cancer is not fully understood but appears to involve multiple genetic changes. We have identified a gene, GC79, that is more highly expressed in androgen-dependent LNCaP-FGC human prostate cancer cells than in androgen-independent LNCaP-LNO human prostate cancer cells. Physiologic levels (0.1 nM:) of androgens repress expression of GC79 messenger RNA (mRNA) in LNCaP-FGC cells. To determine the role of GC79, we cloned its complementary DNA (cDNA) and functionally characterized its product. METHODS: The differentially expressed GC79 gene was cloned from human prostate cDNA libraries, sequenced, and transfected into mammalian cells to study its function. Expression of GC79 was analyzed in various adult and fetal human tissues and in prostate glands of castrated rats. The association of GC79 expression and apoptosis was investigated in COS-1 and LNCaP cells transfected with GC79 cDNA. All statistical tests are two-sided. RESULTS: Sequence analysis indicates that GC79 encodes a large, complex, multitype zinc-finger protein, containing nine C(2)H(2)-type zinc-finger domains, a cysteine-rich region, and a GATA C(4)-type zinc-finger domain. Castration-induced androgen withdrawal increased the expression of GC79 mRNA in the regressing rat ventral prostate, suggesting that the expression of GC79 mRNA is associated with the process of apoptotic cell death in the rat ventral prostate. Transfection and induction of GC79 cDNA in both COS-1 and LNCaP prostate cancer cells led to an apoptotic index that was eightfold higher (P:<.001, two-sided Student's t test) than that observed in uninduced transfected cells. CONCLUSIONS: We have cloned an androgen-repressible gene, GC79, that is potentially involved in apoptosis. This finding may have implications for the development of androgen-independent prostate cancer and, ultimately, for the treatment of prostate cancer

Comparative genomics among cyst nematodes reveals distinct evolutionary histories among effector families and an irregular distribution of effector-associated promoter motifs

JvS, MH and SvdE were supported by a grant from the Applied and Technical Science domain (TTW) of the Netherlands Organization for Scientific Research (NWO) under grant no. 14708. PT received support from the University of St Andrews Bioinformatics Unit (AMD3BIOINF), funded by Wellcome Trust ISSF award 105621/Z/14/Z. MS benefitted from funding by a VENI grant (17282) from the NWO domain Applied and Engineering Sciences.Potato cyst nematodes (PCNs), an umbrella term used for two species, Globodera pallida and G. rostochiensis, belong worldwide to the most harmful pathogens of potato. Pathotype-specific host plant resistances are an essential handle for PCN control. However, the poor delineation of G. pallida pathotypes hampers the efficient use of available host plant resistances. Long-read sequencing technology allowed us to generate a new reference genome of G. pallida population D383 and, as compared to the current reference, the new genome assembly is 42 times less fragmented. For comparison of diversification patterns of six effector families between G. pallida and G. rostochiensis, an additional reference genome was generated for an outgroup, the beet cyst nematode Heterodera schachtii (IRS population). Large evolutionary contrasts in effector family topologies were observed. While VAPs diversified before the split between the three cyst nematode species, the families GLAND5 and GLAND13 only expanded in PCN after their separation from the genus Heterodera. Although DNA motifs in the promoter regions thought to be involved in the orchestration of effector expression ('DOG boxes') were present in all three cyst nematode species, their presence is not a necessity for dorsal gland-produced effectors. Notably, DOG box dosage was only loosely correlated with expression level of individual effector variants. Comparison of the G. pallida genome with those of two other cyst nematodes underlined the fundamental differences in evolutionary history between effector families. Re-sequencing of PCN populations with deviant virulence characteristics will allow for the linking of these characteristics with the composition of the effector repertoire as well as for the mapping of PCN diversification patterns resulting from extreme anthropogenic range expansion.Publisher PDFPeer reviewe

Androgen-independent expression of adrenomedullin and peptidylglycine alpha-amidating monooxygenase in human prostatic carcinoma

Most of the locally advanced and metastatic prostate carcinomas (PCs) treated with antiandrogenic therapy eventually become refractory to this treatment. Locally produced factors may control prostate tumor biology after androgen withdrawal. Adrenomedullin (AM) is expressed in the prostate and could control cell growth in androgen-independent conditions. AM needs to be amidated by the enzyme peptidylglycine alpha-amidating monooxygenase (PAM) to become fully active. The objective of the present study was to analyze whether the expression of preproadrenomedullin (preproAM) and PAM in PC is regulated by androgens. For this purpose, human in vitro and in vivo PC models were grown in the presence or absence of androgens, and the expression of AM and PAM was examined by immunohistochemistry, Western blotting, RT-PCR, and Northern blotting. Furthermore, immunohistochemical analysis of AM in clinical specimens was performed to test if its expression is related to Gleason score and antiandrogenic therapy. In PC cell lines and xenografts, mRNA and protein AM levels were similar in the presence or absence of androgens. PAM expression seemed to be induced by androgen-withdrawal. Our results in clinical samples showed no relationship between AM expression and Gleason score or antiandrogenic treatment. In conclusion, our results demonstrate that preproAM and PAM expression in the human prostate is androgen-independent. In addition, we also report for the first time the expression of a novel PAM transcript in PC, which has not been previously described in other tissues

Simultaneous X-ray and Ultraviolet spectroscopy of the Seyfert galaxy NGC 5548. III. X-ray time variability

The Seyfert 1 galaxy NGC 5548 was observed for a week by Chandra using both the HETGS and LETGS spectrometers. In this paper we study the time variability of the continuum radiation. During our observation, the source showed a gradual increase in flux over four days, followed by a rapid decrease and flattening of the light curve afterwards. Superimposed upon these relatively slow variations several short duration bursts or quasi-periodic oscillations occured with a typical duration of several hours and separation between 0.6-0.9 days. The bursts show a delay of the hard X-rays with respect to the soft X-rays of a few hours. We interprete these bursts as due to a rotating, fluctuating hot spot at approximately 10 gravitational radii; the time delay of the hard X-rays from the bursts agree with the canonical picture of Inverse Compton scattering of the soft accretion disk photons on a hot medium that is relatively close to the central black hole.Comment: 6 pages, 7 figures, accepted for publication in Astronomy and Astrophysic