The partial characterisation of an NFKB homologue from the South African abalone haliotis midae utilising in vivo and in vitro techniques

Includes abstract.Includes bibliographical references (p. 112-116).Haliotis midae is an important marine gastropod that is commercially farmed along the South African coastline. The demand for the edible foot of the abalone far exceeds the supply, as such monitoring the health status of commercially farmed abalone is important if the demand is to be met. In farming conditions, bacterial infections can spread rapidly leading to mass mortalities amongst the abalone population. In order for treatment to be effective, there needs to be an effective monitoring system in place that can assess the health status of the abalone. This study sought to address these issues by identifying a candidate gene that could be an ideal biomarker with respect to a bacterial stress

The progestin-only contraceptive medroxyprogesterone acetate, but not norethisterone acetate, enhances HIV-1 Vpr-mediated apoptosis in human CD4+ T cells through the glucocorticoid receptor

The glucocorticoid receptor (GR) regulates several physiological functions, including immune function and apoptosis. The HIV-1 virus accessory protein, viral protein R (Vpr), can modulate the transcriptional response of the GR. Glucocorticoids (GCs) and Vpr have been reported to induce apoptosis in various cells, including T-cells. We have previously shown that the injectable contraceptive, medroxyprogesterone acetate (MPA) is a partial to full agonist for the GR, unlike norethisterone acetate (NET-A). We investigated the functional cross talk between the GR and Vpr in inducing apoptosis in CD4 + T-cells, in the absence and presence of GCs and these progestins, as well as progesterone. By using flow cytometry, we show that, in contrast to NET-A and progesterone, the synthetic GR ligand dexamethasone (Dex), cortisol and MPA induce apoptosis in primary CD4 + T-cells. Furthermore, the C-terminal part of the Vpr peptide, or HIV-1 pseudovirus, together with Dex or MPA further increased the apoptotic phenotype, unlike NET-A and progesterone. By a combination of Western blotting, PCR and the use of receptor- selective agonists, we provide evidence that the GR and the estrogen receptor are the only steroid receptors expressed in peripheral blood mononuclear cells. These results, together with the findings that RU486, a GR antagonist, prevents Dex-, MPA- and Vpr-mediated apoptosis, provide evidence for the first time that GR agonists or partial agonists increase apoptosis in primary CD4 + T-cells via the GR. We show that apoptotic induction involves differential expression of key apoptotic genes by both Vpr and GCs/MPA. This work suggests that contraceptive doses of MPA but not NET-A or physiological doses of progesterone could potentially accelerate depletion of CD4 + T-cells in a GR-dependent fashion in HIV-1 positive women, thereby contributing to immunodeficiency. The results imply that choice of progestin used in contraception may be critical to susceptibility and progression of diseases such as HIV-1

The injectable-only contraceptive medroxyprogesterone acetate, unlike norethisterone acetate and progesterone, regulates inflammatory genes in endocervical cells via the glucocorticoid receptor

Clinical studies suggest that the injectable contraceptive medroxyprogesterone acetate (MPA) increases susceptibility to infections such as HIV-1, unlike the injectable contraceptive norethisterone enanthate (NET-EN). We investigated the differential effects, molecular mechanism of action and steroid receptor involvement in gene expression by MPA as compared to NET and progesterone (P4) in the End1/E6E7 cell line model for the endocervical epithelium, a key point of entry for pathogens in the female genital mucosa. MPA, unlike NET-acetate (NET-A) and P4, increases mRNA expression of the anti-inflammatory GILZ and IκBα genes. Similarly, MPA unlike NET-A, decreases mRNA expression of the pro-inflammatory IL-6, IL-8 and RANTES genes, and IL-6 and IL-8 protein levels. The predominant steroid receptor expressed in the End1/E6E7 and primary endocervical epithelial cells is the glucocorticoid receptor (GR), and GR knockdown experiments show that the anti-inflammatory effects of MPA are mediated by the GR. Chromatin-immunoprecipitation results suggest that MPA, unlike NET-A and P4, represses pro-inflammatory cytokine gene expression in cervical epithelial cells via a mechanism involving recruitment of the GR to cytokine gene promoters, like the GR agonist dexamethasone. This is at least in part consistent with direct effects on transcription, without a requirement for new protein synthesis. Dose response analysis shows that MPA has a potency of ∼24 nM for transactivation of the anti-inflammatory GILZ gene and ∼4-20 nM for repression of the pro-inflammatory genes, suggesting that these effects are likely to be relevant at injectable contraceptive doses of MPA. These findings suggest that in the context of the genital mucosa, these GR-mediated glucocorticoid-like effects of MPA in cervical epithelial cells are likely to play a critical role in discriminating between the effects on inflammation caused by different progestins and P4 and hence susceptibility to genital infections, given the predominant expression of the GR in primary endocervical epithelial cells

Crop Updates 2004 - Cereals

This session covers twenty eight papers from different authors: PLENARY 1. Declining profitability in continuous cropping systems. Is more wheat the answer on Duplex soil? Dr Wal Anderson, Department of Agriculture 2. Disease implications of extending the wheat phase in low-medium rainfall areas, Dr Vivian Vanstone and Dr Robert Loughman, Department of Agriculture 3. Prolonged wheat phase on duplex soils – where do weeds set the boundary? Vanessa Stewart, Department of Agriculture WHEAT AGRONOMY 4. Management of small grain screenings in wheat, Dr Wal Anderson and Dr Darshan Sharma, Department of Agriculture 5. Agronomic responses of new wheat varieties, Christine Zaicou-Kunesch, Dr Darshan Sharma, Brenda Shackley, Dr Mohammad Amjad, Dr Wal Anderson and Steve Penny,Department of Agriculture 6. Managing wheat yield reduction from wide rows, Dr Mohammad Amjad and Dr Wal Anderson, Department of Agriculture 7. Row spacing and stubble effect on wheat yield and ryegrass seed set, Glen Riethmuller, Department of Agriculture 8. Grain protein management – lessons learnt on the south coast, Jeremy Lemon, Department of Agriculture 9. Unravelling the mysteries of optimum seed rates, Dr Wal Anderson, Dr Darshan Sharma, Brenda Shackley and Mario D’Antuono, Department of Agriculture 10. Agronomic features for growing better wheat – south east agricultural region 2003, Dr Mohammad Amjad, Veronika Reck and Ben Curtis, Department of Agriculture 11. Agronomic responses of new wheat varieties – great southern agricultural region 2003, Brenda Shackley and Judith Devenish, Department of Agriculture 12. Variety specific responses of new wheat varieties – central agricultural region 2003, Dr Darshan Sharma and Dr Wal Anderson, Department of Agriculture 13. Agronomic responses of new wheat varieties – northern agricultural region 2003, Christine Zaicou-Kunesch, Melaine Kupsch and Anne Smith, Department of Agriculture BARLEY AND OAT AGRONOMY 14. Gairdner for high rainfall – where does Baudin fit in? Blakely Paynter, Roslyn Jettnerand Leanne Schulz, Department of Agriculture 15. Oaten hay – varieties and agronomy, Blakely Paynter, Jocelyn Ball and Tom Sweeny, Department of Agriculture NUTRITION 16. In-furrow fungicide applications in liquid fertiliser, Dr Stephen Loss, CSBP Ltd 17. Elemental sulphur as a fertiliser source in Western Australia, Ashleigh Brooks1A, Justin Fuery2, Geoff Anderson3 and Prof Zed Rengel1,1UWA, 2Summit FertilizerFertilisers and 3Department of Agriculture 18. Genetic variation in potassium efficiency of barley, Paul Damon and Prof. Zed Rengel, Faculty of Natural and Agricultural Sciences, UWA 19. Managing protein through strategic N applications, Eddy Pol and Dr Stephen Loss, CSBP Ltd 20. Nitrogen management for wheat in high rainfall cropping areas, Narelle Hill1, Ray Tugwell1, Dr Wal Anderson1, Ron McTaggart1and Nathan Moyes2, 1Department of Agriculture and 2Landmark 21. Flag smut resistance in current WA wheat varieties, John Majewski and Dr Manisha Shankar, Department of Agriculture 22. Rust resistance update for wheat varieties in WA, Dr Manisha Shankar, John Majewski and Jamie Piotrowski, Department of Agriculture PESTS AND DISEASES 23. Stripe rust in WA – where was it and what can we learn from 2003? Dr Robert Loughman and Ciara Beard, Department of Agriculture 24. Foliar disease management – a key factor in the adoption of Baudin and Hamlin barley, Dr Kithsiri Jayasena, Dr Rob Loughman, Kazue Tanaka and Grey Poulish, Department of Agriculture 25. Validating aphid and virus risk forecasts for cereals, Dr Debbie Thackray, Rohan Prince and Dr Roger Jones, Department of Agriculture and Centre for Legumes in Mediterranean Agriculture HARVESTING 26. Swathing Gairdner barley at 30% moisture, Peter Nelson¹ and Nigel Metz², ¹Cooperative Bulk Handling and ² Fitzgerald Biosphere Group MODELLING 27. Development of a web based grower decision aid application for cereal growers, Dr Leisa Armstrong1, Yee Leong (Alex) Yung1and Dr Moin Salam2 1School of Computer and Information Science, Edith Cowan University; and 2Department of Agriculture 28. Wheat varieties updated in ‘Flowering Calculator’ – a model predicting flowering time, Brenda Shackley, Dr David Tennant, Dr Darshan Sharma and Christine Zaicou‑Kunesch, Department of Agricultur

Differential effects of progestogens on HIV-1 replication and host gene expression in primary PBMCs and cervical tissue explants

Includes bibliographical referencesThe synthetic progestogens, medroxyprogesterone acetate (MPA) and norethisterone enanthate (NET-EN),are widely used in developing countries as injectable contraceptives, where disease burden is high.Levonorgestrel (LNG) is a common progestogen used in oral contraceptives and intrauterine devices. Some studies suggest that MPA, unlike NET, increases HIV-1 acquisition in women, while few studies have reported on the effects of LNG on HIV-1 acquisition. Whether MPA, NET and LNG differentially affect HIV-1infection and the expression of key genes relevant to HIV-1 acquisition via differential molecular mechanisms is key to understanding choice of progestogen contraceptive in young women at high risk forHIV-1 acquisition. The central hypothesis of this study is that the differential effects on host gene expression and HIV-1replication by the different progestogens is due to their differential selectivity to towards different steroid receptors, in particular the glucocorticoid receptor (GR). In order to investigate this hypothesis, the regulation of selected genes was investigated in cervical tissue explants from premenopausal, HIV-1negative, and contraception negative women and peripheral blood mononuclear cells (PBMCs) from women, by real time quantitative PCR, western blotting and Luminex assays, in response to physiologically relevant doses of progestogens. Infection assays were performed in the absence and presence of HIV-1using HIV-1BAL-RENILLA or HIVpNL4.3 infectious molecular clones (IMCs). The GR antagonist RU486 or GR siRNA knockdown was used to determine the role of the GR in modulating ligand-specific effects. PBMCs and primary cervical explants were chosen as useful models to assess the direct effects of these progestogens in both the systemic and in the local mucosal immune environments. In PBMCs, MPA like dexamethasone (DEX, a GR specific agonist), showed anti-inflammatory effects, decreasing pro-inflammatory interleukin (IL) 6, IL8 and regulated upon activation, normal T cell expressed and secreted(RANTES) levels and increasing anti-inflammatory glucocorticoid interacting leucine zipper (GILZ) gene expression levels, while NET, progesterone (P4) and LNG did not, after 48 hours. In primary ectocervical tissue explants, DEX, cortisol, MPA and P4 significantly repressed IL6 while only DEX, cortisol and MPA significantly repressed IL8 and increased GILZ gene expression levels after 48 hours. Steroid receptor expression was characterised in both PBMCs and ectocervical explants. GR was the only detectable steroid receptor protein expressed in PBMCs, while ectocervical explants expressed all the steroid receptors. The progesterone and estrogen receptor levels were higher in ectocervical explants from donors that were in the follicular phase compared to ectocervical explants from donors in the luteal phase of the menstrual cycle. In PBMCs, results suggested that differential gene expression by MPA versus NET and P4is mediated via the GR after 48 hours. Furthermore, it was observed that MPA and DEX, unlike NET, LNG and P4 increases HIV-1 replication in viable PBMCs, in the majority of donors. The increase in HIV-1replication in the MPA treated PBMC samples correlated significantly with an increased in IL6 mRNA levels

Human rights and the confinement of people living with dementia in care homes

This paper responds to growing concerns in human rights practice and scholarship about the confinement of people living with dementia in care homes. Moving beyond the existing focus in human rights scholarship on the role of restrictive practices in confinement, the paper broadens and nuances our understanding of confinement by exploring the daily facilitators of confinement in the lives of people with dementia. The paper draws on data from focus groups and interviews with people living with dementia, care partners, aged care workers, and lawyers and advocates about Australian care homes. It argues that microlevel interrelated and compounding factors contribute to human rights abuses of people living with dementia related to limits on freedom of movement and community access of people living with dementia, at times irrespective of the use of restrictive practices. These factors include immobilization and neglect of residents, limited and segregated recreational activities, concerns about duty of care and liability, apprehension of community exclusion, and pathologization and subversion of resistance. It is necessary to challenge the organizational, cultural, economic, and social dynamics that shape day-to-day, microlevel, routine, and compounding factors that remove the agency of people living with dementia and in turn facilitate entrenched and systematic human rights breaches in care homes

Long Non-coding RNAs Mechanisms of Action in HIV-1 Modulation and the Identification of Novel Therapeutic Targets

This review aims to highlight the role of long non-coding RNAs in mediating human immunodeficiency virus (HIV-1) viral replication, latency, disease susceptibility and progression. In particular, we focus on identifying possible lncRNA targets and their purported mechanisms of action for future drug design or gene therapeutics