Epithelial-to-mesenchymal transition (EMT) is associated with tumor initiation, metastasis, and drug resistance. However, the mechanisms underlying these associations are largely unknown. We studied several tumor types to identify the source of EMT gene expression signals and a potential mechanism of resistance to immuno-oncology treatment.
View Article and Find Full Text PDFAn ability to activate latent HIV-1 expression could benefit many HIV cure strategies, but the first generation of latency reversing agents (LRAs) has proven disappointing. We evaluated AKT/mTOR activators as a potential new class of LRAs. Two glycogen synthase kinase-3 inhibitors (GSK-3i's), SB-216763 and tideglusib (the latter already in phase II clinical trials) that activate AKT/mTOR signaling were tested.
View Article and Find Full Text PDFQuiescence is a hallmark of CD4 T cells latently infected with human immunodeficiency virus 1 (HIV-1). While reversing this quiescence is an effective approach to reactivate latent HIV from T cells in culture, it can cause deleterious cytokine dysregulation in patients. As a key regulator of T-cell quiescence, FOXO1 promotes latency and suppresses productive HIV infection.
View Article and Find Full Text PDFThe expansion of CD8CD28 T cells, a population of terminally differentiated memory T cells, is one of the most consistent immunological changes in humans during aging. CD8CD28 T cells are highly cytotoxic, and their frequency is linked to many age-related diseases. As they do not accumulate in mice, many of the molecular mechanisms regulating their fate and function remain unclear.
View Article and Find Full Text PDFTranscriptional latency of HIV is a last barrier to viral eradication. Chromatin-remodeling complexes and post-translational histone modifications likely play key roles in HIV-1 reactivation, but the underlying mechanisms are incompletely understood. We performed an RNAi-based screen of human lysine methyltransferases and identified the SET and MYND domain-containing protein 2 (SMYD2) as an enzyme that regulates HIV-1 latency.
View Article and Find Full Text PDFAim: The aim of this study was to establish a conceptual schema for government purchasing of alcohol and other drug treatment in Australia which could encompass the diversity and variety in purchasing arrangements, and facilitate better decision-maker by purchasers. There is a limited evidence base on purchasing arrangements in alcohol and drug treatment despite the clear impact of purchasing arrangements on both treatment processes and treatment outcomes.
Methods: The relevant health and social welfare literature on purchasing arrangements was reviewed; data were collected from Australian purchasers and providers of treatment giving detailed descriptions of the array of purchasing arrangements.
PAE8 and PAE9 have pectin acetylesterase activity and together remove one-third of the cell wall acetate associated with pectin formation in Arabidopsis leaves. In pae8 and pae9 mutants, substantial amounts of acetate accumulate in cell walls. In addition, the inflorescence stem height is decreased.
View Article and Find Full Text PDFRecent research shows that the effects of oxytocin are more diverse than initially thought and that in some cases oxytocin can directly influence the response to drugs and alcohol. Large individual differences in basal oxytocin levels and reactivity of the oxytocin system exist. This paper will review the literature to explore how individual differences in the oxytocin system arise and examine the hypothesis that this may mediate some of the individual differences in susceptibility to addiction and relapse.
View Article and Find Full Text PDFBackground: High rates of smoking and lower rates of smoking cessation are known to be associated with common mental disorders such as anxiety and depression, and with individual and community measures of socioeconomic status. It is not known to what extent mental illness and socioeconomic status might be jointly associated with smoking behaviour. We set out to examine the relationship between mental illness, measures of socioeconomic disadvantage and both current smoking and smoking cessation rates.
View Article and Find Full Text PDFIssue Addressed: High smoking rates among the disadvantaged lead to inequalities in health, quality-of-life and financial well-being. Non-government social and community service organisations (SCSO) are a promising setting for tobacco control interventions targeting disadvantaged smokers.
Methods: Financial grants were provided to twenty SCSO in New South Wales to support multi-level changes in service culture, smoking related policies and cessation support between 2007 and 2009.
Introduction And Aims: Novel ways of accessing and engaging smokers who are socially and economically disadvantaged may help reduce socioeconomic disparities in smoking rates. This study assessed the feasibility and acceptability of integrating smoking cessation support into usual care at a social and community service organisation (SCSO).
Design And Methods: One SCSO providing a Personal Helpers and Mentors program participated.