31 research outputs found

    The nuclear receptors of Biomphalaria glabrata and Lottia gigantea: Implications for developing new model organisms

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    © 2015 Kaur et al. 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 creditedNuclear receptors (NRs) are transcription regulators involved in an array of diverse physiological functions including key roles in endocrine and metabolic function. The aim of this study was to identify nuclear receptors in the fully sequenced genome of the gastropod snail, Biomphalaria glabrata, intermediate host for Schistosoma mansoni and compare these to known vertebrate NRs, with a view to assessing the snail's potential as a invertebrate model organism for endocrine function, both as a prospective new test organism and to elucidate the fundamental genetic and mechanistic causes of disease. For comparative purposes, the genome of a second gastropod, the owl limpet, Lottia gigantea was also investigated for nuclear receptors. Thirty-nine and thirty-three putative NRs were identified from the B. glabrata and L. gigantea genomes respectively, based on the presence of a conserved DNA-binding domain and/or ligand-binding domain. Nuclear receptor transcript expression was confirmed and sequences were subjected to a comparative phylogenetic analysis, which demonstrated that these molluscs have representatives of all the major NR subfamilies (1-6). Many of the identified NRs are conserved between vertebrates and invertebrates, however differences exist, most notably, the absence of receptors of Group 3C, which includes some of the vertebrate endocrine hormone targets. The mollusc genomes also contain NR homologues that are present in insects and nematodes but not in vertebrates, such as Group 1J (HR48/DAF12/HR96). The identification of many shared receptors between humans and molluscs indicates the potential for molluscs as model organisms; however the absence of several steroid hormone receptors indicates snail endocrine systems are fundamentally different.The National Centre for the Replacement, Refinement and Reduction of Animals in Research, Grant Ref:G0900802 to CSJ, LRN, SJ & EJR [www.nc3rs.org.uk]

    Glycogen Synthase Kinase 3 (GSK3) Inhibitor, SB-216763, Promotes Pluripotency in Mouse Embryonic Stem Cells

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    Canonical Wnt/β-catenin signaling has been suggested to promote self-renewal of pluripotent mouse and human embryonic stem cells. Here, we show that SB-216763, a glycogen synthase kinase-3 (GSK3) inhibitor, can maintain mouse embryonic stem cells (mESCs) in a pluripotent state in the absence of exogenous leukemia inhibitory factor (LIF) when cultured on mouse embryonic fibroblasts (MEFs). MESCs maintained with SB-216763 for one month were morphologically indistinguishable from LIF-treated mESCs and expressed pluripotent-specific genes Oct4, Sox2, and Nanog. Furthermore, Nanog immunostaining was more homogenous in SB-216763-treated colonies compared to LIF. Embryoid bodies (EBs) prepared from these mESCs expressed early-stage markers for all three germ layers, and could efficiently differentiate into cardiac-like cells and MAP2-immunoreactive neurons. To our knowledge, SB-216763 is the first GSK3 inhibitor that can promote self-renewal of mESC co-cultured with MEFs for more than two months

    Resistance to cancer chemotherapy: failure in drug response from ADME to P-gp

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    Predicting proximal health responses to reminders of death: the influence of coping style and health optimism

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    Research derived from terror management theory (TMT) suggests that conscious contemplations of mortality instigate efforts to remove such threatening cognitions from focal attention. Though efforts to manage death concerns in focal attention can positively affect one's health (e.g., engaging in health conscious behavior), such efforts can also negatively affect one's health (e.g., denying vulnerability to disease). The current research explores how individual differences in coping style and health optimism relate to the ways in which people respond to death-related cognitions in focal attention. Study 1 found that adaptive coping was associated with increased health behavioral intentions immediately after death thoughts were made salient (i.e., when death thoughts were still in focal attention) but not after a delay. Study 2 found that immediately after death thoughts were made salient, health optimism was associated with increased disease-detecting behavioral intentions relating to breast cancer. Theoretical and practical implications of these findings are discusse

    Effect of particulate matter, atmospheric gases, temperature, and humidity on respiratory and circulatory diseases’ trends in Lisbon, Portugal

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    This study addresses the significant effects of both well-known contaminants (particles, gases) and less-studied variables (temperature, humidity) on serious, if relatively common, respiratory and circulatory diseases. The area of study is Lisbon, Portugal, and time series of health outcome (daily admissions in 12 hospitals) and environmental data (daily averages of air temperature, relative humidity, PM10, SO2, NO, NO2, CO, and O3) have been gathered for 1999–2004 to ascertain (1) whether concentrations of air pollutants and levels of temperature and humidity do interfere on human health, as gauged by hospital admissions due to respiratory and circulatory ailments; and (2) whether there is an effect of population age in such admissions. In general terms, statistically significant (p?<?0.001) correlations were found between hospital admissions and temperature, humidity, PM10, and all gaseous pollutants except CO and NO. Age appears to influence respiratory conditions in association with temperature, whereas, for circulatory conditions, such an influence likely involves temperature as well as the gaseous pollutants NO2 and SO2.Radiation, Radionuclides and ReactorsApplied Science
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