MUC1 Regulates Cyclin D1 Gene Expression Through p120 Catenin and β-catenin

MUC1 interacts with β-catenin and p120 catenin to modulate WNT signaling. We investigated the effect of overexpressing MUC1 on the regulation of cyclin D1, a downstream target for the WNT/β-catenin signaling pathway, in two human pancreatic cancer cell lines, Panc-1 and S2-013. We observed a significant enhancement in the activation of cyclin D1 promoter-reporter activity in poorly differentiated Panc1.MUC1F cells that overexpress recombinant MUC1 relative to Panc-1.NEO cells, which express very low levels of endogenous MUC1. In stark contrast, cyclin D1 promoter activity was not affected in moderately differentiated S2-013.MUC1F cells that overexpressed recombinant MUC1 relative to S2-013.NEO cells that expressed low levels of endogenous MUC1. The S2-013 cell line was recently shown to be deficient in p120 catenin. MUC1 is known to interact with P120 catenin. We show here that re-expression of different isoforms of p120 catenin restored cyclin D1 promoter activity. Further, MUC1 affected subcellular localization of p120 catenin in association with one of the main effectors of P120 catenin, the transcriptional repressor Kaiso, supporting the hypothesis that p120 catenin relieved transcriptional repression by Kaiso. Thus, full activation of cyclin D1 promoter activity requires β-catenin activation of TCF-lef and stabilization of specific p120 catenin isoforms to relieve the repression of KAISO. Our data show MUC1 enhances the activities of both β-catenin and p120 catenin

Study of 2 beta-decay of Mo-100 and Se-82 using the NEMO3 detector

After analysis of 5797 h of data from the detector NEMO3, new limits on neutrinoless double beta decay of Mo-100 (T-1/2 > 3.1 x 10(23) y, 90% CL) and Se-82 (T-1/2 > 1.4 x 10(23) y, 90% CL) have been obtained. The corresponding limits on the effective majorana neutrino mass are: 1.4 x 10(22) y (90% CL) for Mo-100 and T-1/2 > 1.2 x 10(22) y (90% CL) for Se-82. Corresponding bounds on the Majoron-neutrino coupling constant are < (0.5-0.9) x 10(- 4) and <(0.7-1.6) x 10(- 4). Two-neutrino 2beta-decay half-lives have been measured with a high accuracy, (T1/2Mo)-Mo-100 = [7.68 +/- 0.02(stat) +/- 0.54(syst)] x 10(18) y and (T1/2Se)-Se-82 = [10.3 +/- 0.3(stat) +/- 0.7(syst)] x 10(19) y. (C) 2004 MAIK "Nauka/Interperiodica"

Measurement of double beta decay of ¹⁰⁰Mo to excited states in the NEMO 3 experiment

The double beta decay of ¹⁰⁰Mo to the 0_{1}^{+} and 2_{1}^{+} excited states of ¹⁰⁰Ru is studied using the NEMO 3 data. After the analysis of 8024 h of data the half-life for the two-neutrino double beta decay of ¹⁰⁰Mo to the excited 0_{1}^{+} state is measured to be T_{1/2}^{2v} = [5.7_{-0.9}^{+1.3} (stat.) ± 0.8 (syst.)] x 10²⁰ y. The signal-to-background ratio is equal to 3. Information about energy and angular distributions of emitted electrons is also obtained. No evidence for neutrinoless double beta decay to the excited 0_{1}^{+} state has been found. The corresponding half-life limit is T_{1/2}^{0v} (0⁺→0_{1}^{+}) > 8.9 x 10²² y (at 90% C.L.). The search for the double beta decay to the 2_{1}^{+} excited state has allowed the determination of limits on the half-life for the two neutrino mode T_{1/2}^{0v} (0⁺→2_{1}^{+}) > 1.1 x 10²¹ y (at 90% C.L.) and for the neutrinoless mode T_{1/2}^{0v} (0⁺→2_{1}^{+}) > 1.6 x 10²³ y (at 90% C.L.)

Study of 2b-decay of Mo-100 and Se-82 using the NEMO3 detector

After analysis of 5797 h of data from the detector NEMO3, new limits on neutrinoless double beta decay of Mo-100 (T_{1/2} > 3.1 10^{23} y, 90% CL) and Se-82 (T_{1/2} > 1.4 10^{23} y, 90% CL) have been obtained. The corresponding limits on the effective majorana neutrino mass are: m < (0.8-1.2) eV and m < (1.5-3.1) eV, respectively. Also the limits on double-beta decay with Majoron emission are: T_{1/2} > 1.4 10^{22} y (90% CL) for Mo-100 and T_{1/2}> 1.2 10^{22} y (90%CL) for Se-82. Corresponding bounds on the Majoron-neutrino coupling constant are g < (0.5-0.9) 10^{-4} and < (0.7-1.6) 10^{-4}. Two-neutrino 2b-decay half-lives have been measured with a high accuracy, T_{1/2} Mo-100 = [7.68 +- 0.02(stat) +- 0.54(syst) ] 10^{18} y and T_{1/2} Se-82 = [10.3 +- 0.3(stat) +- 0.7(syst) ] 10^{19} y.Comment: 5 pages, 4 figure

Limits on different Majoron decay modes of 100^{100}Mo and 82^{82}Se for neutrinoless double beta decays in the NEMO-3 experiment

The NEMO-3 tracking detector is located in the Fr\'ejus Underground Laboratory. It was designed to study double beta decay in a number of different isotopes. Presented here are the experimental half-life limits on the double beta decay process for the isotopes $^{100}$Mo and $^{82}$Se for different Majoron emission modes and limits on the effective neutrino-Majoron coupling constants. In particular, new limits on "ordinary" Majoron (spectral index 1) decay of $^{100}$Mo ($T_{1/2} > 2.7\cdot10^{22}$ y) and $^{82}$Se ($T_{1/2} > 1.5\cdot10^{22}$ y) have been obtained. Corresponding bounds on the Majoron-neutrino coupling constant are $< (0.4-1.9) \cdot 10^{-4}$ and $< (0.66-1.7) \cdot 10^{-4}$.Comment: 23 pages includind 4 figures, to be published in Nuclear Physics

Measurement of double beta decay of 100Mo to excited states in the NEMO 3 experiment

The double beta decay of 100Mo to the 0^+_1 and 2^+_1 excited states of 100Ru is studied using the NEMO 3 data. After the analysis of 8024 h of data the half-life for the two-neutrino double beta decay of 100Mo to the excited 0^+_1 state is measured to be T^(2nu)_1/2 = [5.7^{+1.3}_{-0.9}(stat)+/-0.8(syst)]x 10^20 y. The signal-to-background ratio is equal to 3. Information about energy and angular distributions of emitted electrons is also obtained. No evidence for neutrinoless double beta decay to the excited 0^+_1 state has been found. The corresponding half-life limit is T^(0nu)_1/2(0^+ --> 0^+_1) > 8.9 x 10^22 y (at 90% C.L.). The search for the double beta decay to the 2^+_1 excited state has allowed the determination of limits on the half-life for the two neutrino mode T^(2nu)_1/2(0^+ --> 2^+_1) > 1.1 x 10^21 y (at 90% C.L.) and for the neutrinoless mode T^(0nu)_1/2(0^+ --> 2^+_1) > 1.6 x 10^23 y (at 90% C.L.).Comment: 23 pages, 7 figures, 4 tables, submitted to Nucl. Phy

Probing New Physics Models of Neutrinoless Double Beta Decay with SuperNEMO

The possibility to probe new physics scenarios of light Majorana neutrino exchange and right-handed currents at the planned next generation neutrinoless double beta decay experiment SuperNEMO is discussed. Its ability to study different isotopes and track the outgoing electrons provides the means to discriminate different underlying mechanisms for the neutrinoless double beta decay by measuring the decay half-life and the electron angular and energy distributions.Comment: 17 pages, 14 figures, to be published in E.P.J.

"I do what I have to do to survive": An investigation into the perceptions, experiences and economic considerations of women engaged in sex work in Northern Namibia

<p>Abstract</p> <p>Background</p> <p>There is little published research investigating sex work in Namibia, particularly in rural areas. Therefore, the aim of this paper was to determine the views of women engaged in sex work in the Oshakati area of Namibia concerning the main factors influencing their use, or non-use, of male condoms during transactional sexual exchanges.</p> <p>Methods</p> <p>Qualitative interviews were used to better understand the perceptions, experiences and economic considerations of female sex workers in Namibia who were involved in a Behavior Change Communication Program encouraging safer sex practices among high-risk populations in 2006 and 2007.</p> <p>Results</p> <p>While the Behavior Change Communication Program has made significant strides in educating and empowering young women to negotiate more consistent condom use with sexual partners, the gendered economic inequalities and power imbalances within rural and semi-urban Namibian society that favor men hinder further advancement towards positive behavioral change for HIV prevention and also hinder the development of the loving relationships sought by some sex workers.</p> <p>Conclusion</p> <p>This study found that sex workers and transactional sex encounters are heterogeneous entities dependent upon the characteristics of the man (known, stranger, wealthy, attractive to the woman) and the woman (in financial need, desiring love). These features all influence condom use. The 3 E's 'education, empowerment and economic independence' are critical factors needed to encourage and facilitate consistent condom use to prevent HIV transmission. Without financial independence and occupational alternatives building on their health education and empowerment, women who engage in sex work-and transactional sex more generally-will remain largely marginalized from Namibian society, and will continue engaging in risky sexual practices that facilitate HIV acquisition and transmission throughout the community.</p

Results of the BiPo-1 prototype for radiopurity measurements for the SuperNEMO double beta decay source foils

The development of BiPo detectors is dedicated to the measurement of extremely high radiopurity in $^{208}$Tl and $^{214}$Bi for the SuperNEMO double beta decay source foils. A modular prototype, called BiPo-1, with 0.8 $m^2$ of sensitive surface area, has been running in the Modane Underground Laboratory since February, 2008. The goal of BiPo-1 is to measure the different components of the background and in particular the surface radiopurity of the plastic scintillators that make up the detector. The first phase of data collection has been dedicated to the measurement of the radiopurity in $^{208}$Tl. After more than one year of background measurement, a surface activity of the scintillators of $\mathcal{A}$($^{208}$Tl) $=$ 1.5 $\mu$Bq/m$^2$ is reported here. Given this level of background, a larger BiPo detector having 12 m$^2$ of active surface area, is able to qualify the radiopurity of the SuperNEMO selenium double beta decay foils with the required sensitivity of $\mathcal{A}$($^{208}$Tl) $<$ 2 $\mu$Bq/kg (90% C.L.) with a six month measurement.Comment: 24 pages, submitted to N.I.M.

Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser.

G-protein-coupled receptors (GPCRs) signal primarily through G proteins or arrestins. Arrestin binding to GPCRs blocks G protein interaction and redirects signalling to numerous G-protein-independent pathways. Here we report the crystal structure of a constitutively active form of human rhodopsin bound to a pre-activated form of the mouse visual arrestin, determined by serial femtosecond X-ray laser crystallography. Together with extensive biochemical and mutagenesis data, the structure reveals an overall architecture of the rhodopsin-arrestin assembly in which rhodopsin uses distinct structural elements, including transmembrane helix 7 and helix 8, to recruit arrestin. Correspondingly, arrestin adopts the pre-activated conformation, with a ∼20° rotation between the amino and carboxy domains, which opens up a cleft in arrestin to accommodate a short helix formed by the second intracellular loop of rhodopsin. This structure provides a basis for understanding GPCR-mediated arrestin-biased signalling and demonstrates the power of X-ray lasers for advancing the frontiers of structural biology