Gene profiling reveals hydrogen sulphide recruits death signaling via the N-methyl-D-aspartate receptor identifying commonalities with excitotoxicity

Recently the role of hydrogen sulphide (H₂S) as a gasotransmitter stimulated wide interest owing to its involvement in Alzheimer's disease and ischemic stroke. Previously we demonstrated the importance of functional ionotropic glutamate receptors (GluRs) by neurons is critical for H₂S-mediated dose- and time-dependent injury. Moreover N-methyl-D-aspartate receptor (NMDAR) antagonists abolished the consequences of H₂S-induced neuronal death. This study focuses on deciphering the downstream effects activation of NMDAR on H₂S-mediated neuronal injury by analyzing the time-course of global gene profiling (5, 15, and 24 h) to provide a comprehensive description of the recruitment of NMDAR-mediated signaling. Microarray analyses were performed on RNA from cultured mouse primary cortical neurons treated with 200 µM sodium hydrosulphide (NaHS) or NMDA over a time-course of 5–24 h. Data were validated via real-time PCR, western blotting, and global proteomic analysis. A substantial overlap of 1649 genes, accounting for over 80% of NMDA global gene profile present in that of H₂S and over 50% vice versa, was observed. Within these commonly occurring genes, the percentage of transcriptional consistency at each time-point ranged from 81 to 97%. Gene families involved included those related to cell death, endoplasmic reticulum stress, calcium homeostasis, cell cycle, heat shock proteins, and chaperones. Examination of genes exclusive to H₂S-mediated injury (43%) revealed extensive dysfunction of the ubiquitin-proteasome system. These data form a foundation for the development of screening platforms and define targets for intervention in H₂S neuropathologies where NMDAR-activated signaling cascades played a substantial role. J. Cell. Physiol. 226: 1308–1322, 2011.

Apoptosis goes on a chip : advances in the microfluidic analysis of programmed cell death

Recent years have brought enormous progress in cell-based lab-on-a-chip technologies, allowing dynamic studies of cell death with an unprecedented accuracy. As interest in the microfabricated technologies for cell-based bioassays is rapidly gaining momentum, we highlight the most promising technologies that provide a new outlook for the rapid assessment of programmed and accidental cell death and are applicable in drug discovery, high-content drug screening, and personalized clinical diagnostics.

‘Till death do us part : judging the men who kill their intimate partners

This paper examines the construction of masculinity in judge’s sentencing remarks across seventeen cases of male perpetrated intimate femicide sentenced between March 2005 and May 2007 in the Victorian Supreme Court. Using a narrative analysis of sentencing transcripts it investigates how ideal understandings of hegemonic masculinity are used in judicial decision making to condemn or sympathise with male offenders of intimate femicide. The findings illustrate the profound influence that traditional understandings of masculinity and fatherhood still have on current sentencing practises despite the current climate of homicide law reform both within Australia and overseas. Whilst this paper did not directly assess the impact of recent homicide law reforms, specifically provocation, it is explicitly concerned with the continued influence of gender norms and bias at the sentencing stage of the legal process. As such, it provides a preliminary illustration of the key role that judges play in advocating or rejecting change within the criminal justice system, and more broadly legitimising attitudes about male violence against women throughout society. In condoning the use of extreme violence, in any context, judges send a message to society that such behaviour is either generally or specifically acceptable and accommodated within a legal framework.

Flusser's death rattle

A live film performance using magnificent 16mm featuring Dirk De Bruyn in person. Can an image be sonic and ephemeral in the digital age? Live 3-screen film projection, shadow-play and sound poetry plumbing 35 years of experimental film practice, laying bare those processes of graffiti production splattered across the alleyways and railway lines of the planet’s inner cities but whose performance threatens to become completely hidden inside the computer. Images scratched, dyed, bleached and redrawn by hand are brought together to immerse the audience in an aural-visual rant. Does the analogue answer back to the digital media explosion or merely succumb in an angry death rattle of lost causes? Rev presents a rare opportunity to see one of Australia’s most important experimental filmmakers presenting a unique expanded cinema event.

Rich in death, as in life

Dr. Cassandra Atherton's tribute to the late American poet Adrienne Rich, who died aged 82.

Towards a standardised methodology for estimating alcohol-caused death, injury and illness in Australia

Two key methodological issues underlying different methods for calculating estimates of the number of alcohol-caused deaths are identified and recommendations suggested for future work.

1. How to adjust alcohol aetiologic fractions across time and place to reflect different levels of risky drinking. A common approach is outlined for both acute and chronic alcohol-related conditions. In the absence of consistent, reliable and regionally specific measures of the prevalence of risky alcohol consumption from national surveys, the use of per capita consumption data as a means of adjusting alcohol population aetiologic fractions over time and across regions is recommended.

2. Whether abstainers or low-risk drinkers should be used as the reference group when assessing the impact of alcohol consumption and how the resulting information is best presented. It is recommended that when abstainers are used as the reference group, the costs and benefits for both 'low-risk' and 'risky/high-risk' drinking should be identified. Using this approach, it was estimated that for Australia in 1998 there was a net benefit of 5,100 lives saved due to low-risk drinking, while there was a net loss of 2,737 lives due to risky/high-risk drinking. On its own, the figure of a net saving of 2,363 lives per year is a simplistic and potentially misleading picture of alcohol as a net benefit to public health and safety. For public health communications, there is still value in providing estimates using the low-risk drinking contrast, of the number of lives saved if risky/high-risk drinkers all became low-risk drinkers (n=3,292 in 1998). The use of the abstinence contrast, however, allows the more complex picture of alcohol's impact on public health to be apparent, e.g. including the estimated 1,505 deaths associated with low-risk drinking (mostly from cancer).