Characterization of magnesium requirement of human 5'-tyrosyl DNA phosphodiesterase mediated reaction

<p>Abstract</p> <p>Background</p> <p>Topo-poisons can produce an enzyme-DNA complex linked by a 3'- or 5'-phosphotyrosyl covalent bond. 3'-phosphotyrosyl bonds can be repaired by tyrosyl DNA phosphodiesterase-1 (TDP1), an enzyme known for years, but a complementary human enzyme 5'-tyrosyl DNA phosphodiesterase (hTDP2) that cleaves 5'-phosphotyrosyl bonds has been reported only recently. Although hTDP2 possesses both 3'- and 5'- tyrosyl DNA phosphodiesterase activity, the role of Mg²⁺in its activity was not studied in sufficient details.</p> <p>Results</p> <p>In this study we showed that purified hTDP2 does not exhibit any 5'-phosphotyrosyl phosphodiesterase activity in the absence of Mg²⁺/Mn²⁺, and that neither Zn²⁺or nor Ca²⁺can activate hTDP2. Mg²⁺also controls 3'-phosphotyrosyl activity of TDP2. In MCF-7 cell extracts and de-yolked zebrafish embryo extracts, Mg²⁺controlled 5'-phosphotyrosyl activity. This study also showed that there is an optimal Mg²⁺concentration above which it is inhibitory for hTDP2 activity.</p> <p>Conclusion</p> <p>These results altogether reveal the optimal Mg²⁺requirement in hTDP2 mediated reaction.</p

Additive Anti-Tumor Effects of Lovastatin and Everolimus In Vitro through Simultaneous Inhibition of Signaling Pathways

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedThis work was supported by a research grant from the Ludwig-Maximilians University of Munich (Förderprogramm für Forschung und Lehre [FöFoLe], grant number 865/829)

Breastfeeding self-efficacy of women using second-line strategies for healthy term infants in the first week postpartum: an Australian observational study

Background Breastfeeding self-efficacy (BFSE) supports breastfeeding initiation and duration. Challenges to breastfeeding may undermine BFSE, but second-line strategies including nipple shields, syringe, cup, supply line and bottle feeding may support breastfeeding until challenges are resolved. The primary aim of this study was to examine BFSE in a sample of women using second-line strategies for feeding healthy term infants in the first week postpartum. Methods A retrospective self-report study was conducted using the Breastfeeding Self-Efficacy Scale - Short Form (BSES-SF), demographic and infant feeding questionnaires. Breastfeeding women who gave birth to a singleton healthy term infant at one private metropolitan birthing facility in Australia from November 2008 to February 2009 returned anonymous questionnaires by mail. Results A total of 128 (73 multiparous, 55 primiparous) women participated in the study. The mean BSES-SF score was 51.18 (Standard deviation, SD: 12.48). The median BSES-SF score was 53. Of women using a second-line strategy, 16 exceeded the median, and 42 were below. Analyses using Kruskal-Wallis tests confirmed this difference was statistically significant (H = 21.569, p = 0.001). The rate of second-line strategy use was 48%. The four most commonly used second-line strategies were: bottles with regular teats (77%); syringe feeding (44%); bottles with wide teats (34%); and nipple shields (27%). Seven key challenges were identified that contributed to the decision to use second-line strategies, including: nipple pain (40%); unsettled infant (40%); insufficient milk supply (37%); fatigue (37%); night nursery care (25%); infant weight loss > 10% (24%); and maternal birth associated pain (20%). Skin-to-skin contact at birth was commonly reported (93%). At seven days postpartum 124 women (97%) were continuing to breastfeed. Conclusions The high rate of use of second-line strategies identified in this study and high rate of breastfeeding at day seven despite lower BFSE indicate that such practices should not be overlooked by health professionals. The design of this study does not enable determination of cause-effect relationships to identify factors which contribute to use of second-line strategies. Nevertheless, the significantly lower BSES-SF score of women using a second-line strategy highlights this group of women have particular needs that require attention