Effect of arsenic on transcription factor AP-1 and NF-kB DNA binding activity and related gene expression

Both acute (24 h) and chronic (10–20 week) exposure of human fibroblast cells to low dose sodium arsenite (As(III)) significantly affects activating protein-1 (AP-1) and nuclear factor kappa B (NF-κB) DNA binding activity. Short-term treatment with 0.1–5 μM As(III) up-regulates expression of c-Fos and c-Jun and the redox regulators, thioredoxin (Trx) and Redox factor-1 (Ref-1) and activates both AP-1 and NF-κB binding. Chronic exposure to 0.1 or 0.5 μM As(III) decreased c-Jun, c-Fos and Ref-1 protein levels and AP-1 and NF-κB binding activity, but increased Trx expression. Short term exposure to phorbol 12-myristate 13-acetate (TPA), a phorbol ester tumour promoter, or hydrogen peroxide (H₂O₂) also activates AP-1 and NF-κB binding. However, pre-treatment with As(III) prevents this increase. These results suggest that As(III) may alter AP-1 and NF-κB activity, in part, by up-regulating Trx and Ref-1. The different effects of short- versus long-term As(III) treatment on acute-phase response to oxidative stress reflect changes in the expression of Ref-1, c-Fos and c-Jun, but not Trx.

RTKN2 induces NF-KappaB dependent resistance to intrinsic apoptosis in HEK cells and REgulates BCL-2 genes in human CD4+ lymphocytes

The gene for Rhotekin 2 (RTKN2) was originally identified in a promyelocytic cell line resistant to oxysterol-induced apoptosis. It is differentially expressed in freshly isolated CD4+ T-cells compared with other hematopoietic cells and is down-regulated following activation of the T-cell receptor. However, very little is known about the function of RTKN2 other than its homology to Rho-GTPase effector, rhotekin, and the possibility that they may have similar roles. Here we show that stable expression of RTKN2 in HEK cells enhanced survival in response to intrinsic apoptotic agents; 25-hydroxy cholesterol and camptothecin, but not the extrinsic agent, TNFα. Inhibitors of NF-KappaB, but not MAPK, reversed the resistance and mitochondrial pro-apoptotic genes, Bax and Bim, were down regulated. In these cells, there was no evidence of RTKN2 binding to the GTPases, RhoA or Rac2. Consistent with the role of RTKN2 in HEK over-expressing cells, suppression of RTKN2 in primary human CD4+ T-cells reduced viability and increased sensitivity to 25-OHC. The expression of the pro-apoptotic genes, Bax and Bim were increased while BCL-2 was decreased. In both cell models RTKN2 played a role in the process of intrinsic apoptosis and this was dependent on either NF-KappaB signaling or expression of downstream BCL-2 genes. As RTKN2 is a highly expressed in CD4+ T-cells it may play a role as a key signaling switch for regulation of genes involved in T-cell survival.

Doing what your big sister does : sex, postfeminism and the YA chick lit series

Mass-marketed teen chick lit has become a publishing phenomenon and has begun to attract critical interest among children’s literature scholars. Much of this critical work, however, has shied away from robust critical assessment of the postfeminist conditions informing the production and reception of young adult series like Private, Gossip Girl and Choose Your Own Destiny. Existing analyses may nod to the origins of the genre in women’s chick lit, but do not investigate how the postfeminist construction of ‘empowered’ female (hetero) sexuality translates into chick lit for young adults. Paying particular attention to these issues, this paper draws on feminist critiques of postfeminism to interrogate the implications of the way these novels position readers to understand their sexuality. In doing so, it poses postfeminist criticism as an unconsidered yet significant framework to evaluate novels for teenage girls.

Invitation to the feed: the body and the environment in a selection of dystopian YA science fictions

 In an analysis of Monica Hughes’ Invitation to the Game and M. T. Anderson’s Feed, this paper explores the nexus between nature and the artificial, and how that both empowers and disempowers young adults in two highly technological futuristic dystopias.

"I tell ya who needs educatin’”: non-Indigenous cultural self-awareness and prisoner education.

Glen says, “current education is colonial; it ain’t ours. I tell ya who needs educatin’, wadjellas”. Glen is a Noongar man who, along with several other Aboriginal adults living in Western Australia, teaches me in a PhD research project about prisoner education from their perspective. His words pose a question for wadjellas like myself who are raised, taught and work in a white neo-colonial society. We have been raised in, taught in and work in a colonial system. As non-Aboriginal people we have unearned privileges which are often invisible and unacknowledged. How then to address the outcomes of this in a way that might lead to working co-operatively alongside Aboriginal people? What kind of ‘educatin’ could teach us about our own unacknowledged privilege and the disadvantage this can lead to for others? Is the standard cross-cultural awareness training enough?This paper shares some of the teachings of Glen and other participants in this research. It expresses the view that, ultimately, the usually unacknowledged legacy of colonisation and associated issue of denied Aboriginal sovereignty lies at the heart of much of the disadvantage experienced by Aboriginal people today when considering education and the prison system. Addressing gaps in non-Indigenous cultural self-awareness by learning from Aboriginal people is an important factor in improving their experiences of education.