Bioaccumulation of PCB & DDE methyl sulfones in marine mammals and their interactions with receptor proteins

PCB and DDE-Methyl sulphone metabolites are the product of enzymatic and bile acid entero hepatic metabolism in the final phase (III) of PCB and DDE detoxification in mammals following hepatic microsomal cytochrome P450-dependent metabolism (phase I) and conjugation (phase II). There is good evidence that PCB and DDE methyl sulphone (MSF) metabolites interfere with steroid binding to a receptor protein in uterine epithelium (uteroglobin - UG2 and bronchial epithelium (clara cell secretory protein - CCSP). UG and CCSP are homologous 16,000 Da proteins with different tissue-specific functions. UG binds progesterone in the pre-implantation uterus to signal localised endometrial thickening and capillary formation, vital for successful attachment of the fertilised embryo. PCB-MSFs can displace progesterone in the mammalian uterus due to their higher affinity for UG, resulting in implantation failure or early fetal death. CCSP however, functions to sequester phospholipase A2 (PLA2) released in response to stress (pathogenic infection / injury) to suppress inflammatory responses triggered by PLA2 in bronchial epithelium. CCSP is also known as retinol-binding protein (RBP) transporting retinol (vit A) to target epithelia for a functional immune response*. Studies with Harbour Seals demonstrated displacement of retinol from RBP by hydroxy-PCB metabolites resulting in immunosuppression. PCB-MSFs have been shown to accumulate in clara cells and uterine epithelium in laboratory radioactive tracer studies and CCSP-knock out studies with mice. PCB and DDE -MSFs burdens have been found in marine mammals, suggesting they may be subject to reproductive and immuno-toxic effects of these metabolites. This study determines PCB and DDE-MSFs burdens in tissues (including lung & uterus) of Harbour Seal (Phoca vitulina) and Striped Dolphin (Stenella coeruleoalba) morbillivirus victims and characterises the marine mammalian UG/CCSP protein

Doubly heavy spin--1/2 baryon spectrum in QCD

We calculate the mass and residue of the heavy spin--1/2 baryons containing two heavy b or c quarks in the framework of QCD sum rules. We use the most general form of the interpolating current in its symmetric and anti-symmetric forms with respect to the exchange of heavy quarks, to calculate the two-point correlation functions describing the baryons under consideration. A comparison of the obtained results with existing predictions from various approaches is also made.Comment: 17 Pages, 2 Figures and 2 Table

Who knows best? A Q methodology study to explore perspectives of professional stakeholders and community participants on health in low-income communities

Abstract Background Health inequalities in the UK have proved to be stubborn, and health gaps between best and worst-off are widening. While there is growing understanding of how the main causes of poor health are perceived among different stakeholders, similar insight is lacking regarding what solutions should be prioritised. Furthermore, we do not know the relationship between perceived causes and solutions to health inequalities, whether there is agreement between professional stakeholders and people living in low-income communities or agreement within these groups. Methods Q methodology was used to identify and describe the shared perspectives (‘subjectivities’) that exist on i) why health is worse in low-income communities (‘Causes’) and ii) the ways that health could be improved in these same communities (‘Solutions’). Purposively selected individuals (n = 53) from low-income communities (n = 25) and professional stakeholder groups (n = 28) ranked ordered sets of statements – 34 ‘Causes’ and 39 ‘Solutions’ – onto quasi-normal shaped grids according to their point of view. Factor analysis was used to identify shared points of view. ‘Causes’ and ‘Solutions’ were analysed independently, before examining correlations between perspectives on causes and perspectives on solutions. Results Analysis produced three factor solutions for both the ‘Causes’ and ‘Solutions’. Broadly summarised these accounts for ‘Causes’ are: i) ‘Unfair Society’, ii) ‘Dependent, workless and lazy’, iii) ‘Intergenerational hardships’ and for ‘Solutions’: i) ‘Empower communities’, ii) ‘Paternalism’, iii) ‘Redistribution’. No professionals defined (i.e. had a significant association with one factor only) the ‘Causes’ factor ‘Dependent, workless and lazy’ and the ‘Solutions’ factor ‘Paternalism’. No community participants defined the ‘Solutions’ factor ‘Redistribution’. The direction of correlations between the two sets of factor solutions – ‘Causes’ and ‘Solutions’ – appear to be intuitive, given the accounts identified. Conclusions Despite the plurality of views there was broad agreement across accounts about issues relating to money. This is important as it points a way forward for tackling health inequalities, highlighting areas for policy and future research to focus on

Ozone Depletion from Nearby Supernovae

Estimates made in the 1970's indicated that a supernova occurring within tens of parsecs of Earth could have significant effects on the ozone layer. Since that time, improved tools for detailed modeling of atmospheric chemistry have been developed to calculate ozone depletion, and advances have been made in theoretical modeling of supernovae and of the resultant gamma-ray spectra. In addition, one now has better knowledge of the occurrence rate of supernovae in the galaxy, and of the spatial distribution of progenitors to core-collapse supernovae. We report here the results of two-dimensional atmospheric model calculations that take as input the spectral energy distribution of a supernova, adopting various distances from Earth and various latitude impact angles. In separate simulations we calculate the ozone depletion due to both gamma-rays and cosmic rays. We find that for the combined ozone depletion roughly to double the ``biologically active'' UV flux received at the surface of the Earth, the supernova must occur at <8 pc. Based on the latest data, the time-averaged galactic rate of core-collapse supernovae occurring within 8 pc is ~1.5/Gyr. In comparing our calculated ozone depletions with those of previous studies, we find them to be significantly less severe than found by Ruderman (1974), and consistent with Whitten et al. (1976). In summary, given the amplitude of the effect, the rate of nearby supernovae, and the ~Gyr time scale for multicellular organisms on Earth, this particular pathway for mass extinctions may be less important than previously thought.Comment: 24 pages, 4 Postscript figures, to appear in The Astrophysical Journal, 2003 March 10, vol. 58

Ageing of enteric neurons: oxidative stress, neurotrophic factors and antioxidant enzymes

Background: Ageing is associated with gastrointestinal dysfunction, which can have a major impact on quality of life of the elderly. A number of changes in the innervation of the gut during ageing have been reported, including neuronal loss and degenerative changes. Evidence indicates that reactive oxygen species (ROS) are elevated in ageing enteric neurons, but that neurotrophic factors may reduce generation of neuronal ROS. Two such factors, glial cell line derived neurotrophic factor (GDNF) and neurotrophin-3 (NT-3) have also been found to protect enteric neurons against oxidative stress induced cell death of enteric ganglion cells in vitro. We have investigated the possible roles of neurotrophic factors further, by examining their expression in the gut during ageing, and by analysing their effects on antioxidant enzyme production in cultures of enteric ganglion cells. Results: Analysis of the expression of GDNF and its receptors c-Ret and GFR α − 1 in rat gut by RT-PCR showed that expression continues throughout life and into ageing, in both ad libitum(AL) and calorically-restricted (CR) animals. Levels of expression of GDNF and GFR α − 1 were elevated in 24 month AL animals compared to 24 month CR animals, and to 24 CR and 6 month control animals respectively. The related factor Neurturin and its receptor GFR α − 2 were also expressed throughout life, the levels of the GFR – α-2(b) isoform were reduced in 24 m AL animals. Immunolabelling showed that c-Ret and GFR α − 1 proteins were expressed by myenteric neurons in ageing animals. GDNF, but not NT-3, was found to increase expression of Cu/Zn superoxide dismutase and catalase by cultured enteric ganglion cells. Conclusions: The neurotrophic factors GDNF and neurturin and their receptors continue to be expressed in the ageing gut. Changes in the levels of expression of GDNF , GFR α-1 and GFR α-2(b) isoform occurred in 24 m AL animals. GDNF, but not NT-3, increased the levels of antioxidant enzymes in cultured enteric ganglion cells, indicating a possible mechanism for the reported protective effect of GDNF against menadione-induced neuronal apoptosis in the ageing gut. Together these data suggest that GDNF family members may play a protective role in the gut throughout life, and support the suggestion that dysregulation of neurotrophic factor support could contribute to neuronal ageing in the gut