Differential Modulation of Transcriptional Activity of Estrogen Receptors by Direct Protein-Protein Interactions with the T Cell Factor Family of Transcription Factors

Two major signaling pathways, those triggered by estrogen (E(2)) and by the Wnt family, interact in the breast to cause growth and differentiation. The estrogen receptors ER(alpha) and ER(beta) are activated by binding E(2) and act as ligand-dependent transcription factors. The effector for the Wnt family is the Tcf family of transcription factors. Both sets of transcription factors recognize discrete but different nucleotide sequences in the promoters of their target genes. By using transient transfections of reporter constructs for the osteopontin and thymidine kinase promoters in rat mammary cells, we show that Tcf-4 antagonizes and Tcf-1 stimulates the effects of activated ER/E(2). For mutants of the former promoter, the stimulatory effects of ER(alpha)/E(2) can be made to be dependent on Tcf-1, and for the latter promoter the effects of the T cell factors (TCFs) are dependent on ER/E(2). Direct interaction between ERs and Tcfs either at the Tcf/ER(alpha)-binding site on the DNA or in the absence of DNA is established by gel retardation assays or by coimmunoprecipitation/biosensor methods, respectively. These results show that the two sets of transcription factors can interact directly, the interaction between ERs and Tcf-4 being antagonistic and that between ERs and Tcf-1 being synergistic on the activity of the promoters employed. Since Tcf-4 is the major Tcf family member in the breast, it is suggested that the antagonistic interaction is normally dominant in vivo in this tissue.

The distribution of Fasciola hepatica and Fasciola gigantica within southern Tanzania - constraints associated with the intermediate host

In East Africa, Fasciola gigantica is generally the causative agent of fasciolosis but there have been reports of F. hepatica in cattle from highland regions of Kenya, Ethiopia, Uganda and Zaire. The topography of the Southern Highlands of Tanzania provides an environment where the climatic conditions exist for the sustenance of lymnaeid species capable of Supporting both Fasciola hepatica and F. gigantica. Theoretically this would allow interaction between fasciolid species and the possible creation of hybrids. In this report we present molecular data confirming the existence of the snail, Lymnaea truncatula, at high altitude on the Kitulo Plateau of the Southern Highlands, Tanzania, along with morphometric and molecular data confirming the presence of F. hepatica in the corresponding area. At lower altitudes, where climatic conditions were unfavourable for the existence of L. truncatula, the presence of its sister species L. natalensis was confirmed by molecular data along with its preferred fasciolid parasite, F. gigantica. Analysis based on a 618 bp sequence of the 28S rRNA gene did not reveal the presence of hybrid fasciolids in our fluke samples.

Does chronic illness place constraints on positive constructions of identity? Temporal comparisons and self-evaluations in people with schizophrenia

It is often suggested that people in potentially threatening situations might engage in self-enhancing temporal comparisons that allow them to view themselves and their experience in a more positive light. Data from semistructured interviews with 12 individuals in the UK diagnosed as having schizophrenia were content analyzed to explore patterns of temporal comparison. The study found that the onset of schizophrenic symptoms created a new baseline in participants' representations of their past, with different types of temporal comparisons occurring before and after this point. Although comparisons with past selves after onset supported the suggestion that people may select and construct their past in such a manner that permits them to see their present circumstances more positively and envisage a better future, comparisons with past selves before onset were more negative. The findings suggest that the Theory of Temporal Self-Appraisals (Ross I Wilson, 2000) needs to be elaborated to include people who have experienced major life changes. (c) 2004 Elsevier Ltd. All rights reserved.

Differential expression of steroid 5 alpha-reductase isozymes and association with disease severity and angiogenic genes predict their biological role in prostate cancer

The biological role of steroid 5 alpha-reductase isozymes (encoded by the SRD5A1 and SRD5A2 genes) and angiogenic factors that play important roles in the pathogenesis and vascularization of prostate cancer (PC) is poorly understood. The sub-cellular expression of these isozymes and vascular endothelial growth factor (VEGF) in PC tissue microarrays (n=62) was examined using immunohistochemistry. The effect of SRD5A inhibition on the angiogenesis pathway genes in PC was also examined in prostate cell lines, LNCaP, PC3, and RWPE-1, by treating them with the SRD5A inhibitors finasteride and dutasteride, followed by western blot, quantitative PCR, and ELISA chip array techniques. In PC tissues, nuclear SRD5A1 expression was strongly associated with higher cancer Gleason scores (P=0.02), higher cancer stage (P=0.01), and higher serum prostate specific antigen (PSA) levels (P=0.01), whereas nuclear SRD5A2 expression was correlated with VEGF expression (P=0.01). Prostate tumor cell viability was significantly reduced in dutasteride-treated PC3 and RWPE-1 cells compared with finasteride-treated groups. Expression of the angiogenesis pathway genes transforming growth factor beta 1 (TGFB1), endothelin (EDN1), TGF alpha (TGFA), and VEGFR1 was upregulated in LNCaP cells, and at least 7 out of 21 genes were upregulated in PC3 cells treated with finasteride (25 mu M). Our findings suggest that SRD5A1 expression predominates in advanced PC, and that inhibition of SRD5A1 and SRD5A2 together was more effective in reducing cell numbers than inhibition of SRD5A2 alone. However, these inhibitors did not show any significant difference in prostate cell angiogenic response. Interestingly, some angiogenic genes remained activated after treatment, possibly due to the duration of treatment and tumor resistance to inhibitors. Endocrine-Related Cancer (2010) 17 757-770

ABSOLUTE DOUBLY DIFFERENTIAL CROSS-SECTIONS FOR ELECTRON-EMISSION IN COLLISIONS OF 3.5-MEV/U FE(17+) AND FE(22+) IONS WITH HE AND AR GAS TARGETS

Absolute doubly differential cross sections have been measured as a function of electron energy and angle of observation for electron emission in collisions of 3.5-MeV/u Fe17+ and Fe22+ ions with He and Ar gas targets under single-collision conditions. The measured electron emission cross sections are compared to theoretical and scaled cross sections based on the Born approximation. The results using intermediate-mass ions are discussed with reference to previously reported cross sections from collisions with highly charged lighter- and heavier-ion species at MeV/u projectile energies. The continuum-distorted-wave-eikonal-initial-state approximation shows good agreement with experiments except in the

Differential Associations of Job Control Components With Mortality: A Cohort Study, 1986-2005

Inconsistent evidence of the hypothesized favorable effects of high job control on health may have resulted from a failure to treat job control as a multifactor concept. The authors studied whether the 2 components of job control, decision authority and skill discretion, were differentially associated with cause-specific mortality in 13,510 Finnish forest company employees with no history of severe illness. Surveys on work characteristics were carried out in 1986 and 1996, and the respondents were followed up until the end of 2005 by use of the Statistics Finland National Death Registry. During a mean follow-up of 15.5 years, 981 participants died. In the analyses adjusted for confounders, employees with high and intermediate levels of skill discretion had a lower all-cause mortality risk than those with low skill discretion, with hazard ratios of 0.84 (95% confidence interval (CI): 0.69, 1.02) and 0.81 (95% CI: 0.69, 0.96), respectively. In contrast, high decision authority was associated with elevated risks of all-cause, cardiovascular, and alcohol-related mortality, with hazard ratios of 1.28 (95% CI: 1.06, 1.54), 1.49 (95% CI: 1.11, 2.02), and 2.03 (95% CI: 1.03, 4.00), respectively. The results suggest that job control is not an unequivocal concept in relation to mortality; decision authority and skill discretion show different and to some extent opposite associations.