Bioengineered 3D platform to explore cell-ECM interactions and drug resistance of epithelial ovarian cancer cells

The behaviour of cells cultured within three-dimensional (3D) structures rather than onto two-dimensional (2D) culture plastic more closely reflects their in vivo responses. Consequently, 3D culture systems are becoming crucial scientific tools in cancer cell research. We used a novel 3D culture concept to assess cell-matrix interactions implicated in carcinogenesis: a synthetic hydrogel matrix equipped with key biomimetic features, namely incorporated cell integrin-binding motifs (e.g. RGD peptides) and the ability of being degraded by cell-secreted proteases (e.g. matrix metalloproteases). As a cell model, we chose epithelial ovarian cancer, an aggressive disease typically diagnosed at an advanced stage when chemoresistance occurs. Both cell lines used (OV-MZ-6, SKOV-3) proliferated similarly in 2D, but not in 3D. Spheroid formation was observed exclusively in 3D when cells were embedded within hydrogels. By exploiting the design flexibility of the hydrogel characteristics, we showed that proliferation in 3D was dependent on cell-integrin engagement and the ability of cells to proteolytically remodel their extracellular microenvironment. Higher survival rates after exposure to the anti-cancer drug paclitaxel were observed in cell spheroids grown in hydrogels (40-60%) compared to cell monolayers in 2D (20%). Thus, 2D evaluation of chemosensitivity may not reflect pathophysiological events seen in patients. Because of the design flexibility of their characteristics and their stability in long-term cultures (28 days), these biomimetic hydrogels represent alternative culture systems for the increasing demand in cancer research for more versatile, physiologically relevant and reproducible 3D matrices.

Highly efficient, stoichiometric radical exchange reactions using isoindoline profluorescent nitroxides

Exchange reactions between the isoindoline profluorescent nitroxide 1,1,3,3-tetramethyldibenzo[e,g]isoindolin-2-yloxyl (TMDBIO) and a TEMPO capped polystyrene were carried out. High conversions to the desired products were achieved using only stoichiometric ratios of nitroxide relative to polymer. The scope of this study was expanded by exploiting a di-nitroxide 9,10-bis(5-[1,1,3,3-tetramethylisoindolin-2-yloxy])anthracene (BTMIOA) as a connector between two polymer chains forming PS–nitroxide–PS systems.

Vitamin D and injury prevention

Vitamin D, along with calcium, may help decrease the risk of falls and fractures in older adults. Sunlight and other sources of ultraviolet radiation are not recommended because they increase the risk of skin cancers and sun-induced eye disorders. Rather, vitamin D and calcium needs should be met through foods and dietary supplements. As a preventive measure to reduce the risk of falls and fractures, it is recommended that older adults meet the 2005 Dietary Guidelines and consume 1000 IU of vitamin D, preferably as vitamin D3.

The application of profluorescent nitroxides to detect reactive oxygen species derived from combustion-generated particulate matter: Cigarette smoke – a case study

Reactive oxygen species (ROS) and related free radicals are considered to be key factors underpinning the various adverse health effects associated with exposure to ambient particulate matter. Therefore, measurement of ROS is a crucial factor for assessing the potential toxicity of particles. In this work, a novel profluorescent nitroxide, BPEAnit, was investigated as a probe for detecting particle-derived ROS. BPEAnit has a very low fluorescence emission due to inherent quenching by the nitroxide group, but upon radical trapping or redox activity, a strong fluorescence is observed. BPEAnit was tested for detection of ROS present in mainstream and sidestream cigarette smoke. In the case of mainstream cigarette smoke, there was a linear increase in fluorescence intensity with an increasing number of cigarette puffs, equivalent to an average of 101 nmol ROS per cigarette based on the number of moles of the probe reacted. Sidestream cigarette smoke sampled from an environmental chamber exposed BPEAnit to much lower concentrations of particles, but still resulted in a clearly detectible increase in fluorescence intensity with sampling time. It was calculated that the amount of ROS was equivalent to 50 ± 2 nmol per mg of particulate matter; however, this value decreased with ageing of the particles in the chamber. Overall, BPEAnit was shown to provide a sensitive response related to the oxidative capacity of the particulate matter. These findings present a good basis for employing the new BPEAnit probe for the investigation of particle-related ROS generated from cigarette smoke as well as from other combustion sources.

The 'Dirty Work' of the Lie

The panel "Duplicity/Complicity: Performing and Misperforming Lies" at PSi #15 in Croatia in July 2009 examined the half-truths, hidden assumptions and power relations embedded in every act of performance through an analysis of the way bodies, buildings, personae and communities perform and misperform lies. It was a collection of new academic voices from Australia and Croatia, intersecting and colliding and, at times, outright lying, with each other and with commentary from Alan Read. Inspired by this successful adventure in collaborative academic mis-performance, "The ‘Dirty Work’ of the Lie" takes the challenge set by the Prelude Panel at PSI #15 and subjects the ideas emerging from this panel to "friendly fire" in order to build a multi authored response to 'performance that lies', with reference to the work of A Chorus of Women, disabled artists Bill Shannon, Aaron Williamson and Kathryn Araneillo, US dance performer Ann Liv Young and US theatre and festival director Peter Sellars. In doing so, "The 'Dirty Work' of the Lie" provides a reflexive response to the duplicity inherent in the performances, and also in our own academic analyses. With Alan Read acting as interlocutor, each contributor will creatively respond to a paper presented by another, developing the key intersecting issues that emerged through the formation of the panel. These issues include impression management, self-belief and performers who are 'taken in by their own act', the dirty work of taking others in with an act, the guerrilla dimension of lying, the productivity of the lie, and questions of audience engagement and ethics. As a result, this new paper tests how the 'misperformance' of lies across different cultural sites, be it deliberate or accidental, can become a productive – and, indeed, politicised – aspect of cultural performance, betraying accepted attitudes, ideas and structures of authority and offering alternative visions. Through it’s distinctively multi vocal texture, "The 'Dirty Work' of the Lie" also interrogates the modes of analysis available to us, questioning the 'duplicity' in our reflecting, responding and listening to each other as well as the work.

Evangeline Series : An interpretation of Classic Gothic Lolita

This series comprises three artefacts described below: Evangeline: Classic Gothic Lolita [3 piece garment]. Evangeline 2: Classic Gothic Lolita Pullip Doll Costume [2 piece garment]. Evangeline 3: Classic Gothic Lolita Mini Pullip Doll Costume [3 piece garment]. The series was part of an exhibition curated by Kathryn Hardy Bernal entitled: "Loli-Pop: A downtown Auckland view on Japanese street fashion". The exhibition explored the connections between gothic lolita fashion and popular culture. This work reflects on the aspect of collections in respect of the work of Hardy Bernal in relation to the connection between the japanese classic gothic lolita and the doll culture surrounding the movement. The pieces are interconnected and intended to communicate these aspects through a doll like dress worn by a model (Evangeline 1], carrying a doll wearing the same dress [Evangeline 2], carrying a smaller doll again wearing the same dress [Evangeline 3]. The artefacts appeared appeared as a central piece in the exhibition which was held at the War Memorial Museum in Auckland, New Zealand (15 September - 25 November 2007).

Lolipop: A downtown Auckland view on Japanese street fashion

Loli-Pop brings together the relationships between the Loli-Goth and popular culture, and the strong association of the Loli-Goth with the doll, including a selection from Hardy Bernal’s personal collection of Japanese Lolita dolls. This display is supported by the highlight of the show, five full-sized garments created and constructed by AUT University Fashion staff members, Angie Finn, Yvonne Stewart, Lize Niemczyk, Gabriella Trussardi, Carmel Donnelly and Kathryn Hardy Bernal, which demonstrate the designers’ own interpretations of Gothic & Lolita, inspired by Japanese street style. The exhibit is complimented by a backdrop of photographs that illustrate the impact of the outfits when worn, modelled by AUT University Bachelor of Fashion Design students, Emily Huang, Shangshang Cookie Wang, Emily Wang, Shiahug-Wen Sean Kuo and Yanling Wang.

Increased traffic exposure and negative birth outcomes : a prospective cohort in Australia

Background: Pregnant women exposed to traffic pollution have an increased risk of negative birth outcomes. We aimed to investigate the size of this risk using a prospective cohort of 970 mothers and newborns in Logan, Queensland. ----- ----- Methods: We examined two measures of traffic: distance to nearest road and number of roads around the home. To examine the effect of distance we used the number of roads around the home in radii from 50 to 500 metres. We examined three road types: freeways, highways and main roads.----- ----- Results: There were no associations with distance to road. A greater number of freeways and main roads around the home were associated with a shorter gestation time. There were no negative impacts on birth weight, birth length or head circumference after adjusting for gestation. The negative effects on gestation were largely due to main roads within 400 metres of the home. For every 10 extra main roads within 400 metres of the home, gestation time was reduced by 1.1% (95% CI: -1.7, -0.5; p-value = 0.001).----- ----- Conclusions: Our results add weight to the association between exposure to traffic and reduced gestation time. This effect may be due to the chemical toxins in traffic pollutants, or because of disturbed sleep due to traffic noise.

A profluorescent azaphenalene nitroxide for nitroxide-mediated polymerization

A novel nitroxide-mediated polymerization (NMP) control agent; 1,1,3,3-tetramethyl-2,3-dihydro-2-azaphenalen-2-yloxyl (TMAO), was used in the free-radical polymerization of styrene. The conversion of styrene during NMP was studied using FT-Raman spectroscopy and the effectiveness of TMAO as a NMP control agent was assessed by GPC analysis. Fidelity of the TMAO-alkoxyamine end-group on the synthesized polymers was confirmed by GPC, UV-Vis and fluorescence spectroscopic analyses. Comparison to the well known NMP control agent, TEMPO was made. TMAO showed control of molecular weight approaching that of TEMPO. Attempts to improve the properties of TMAO as an NMP control agent by synthesizing an analogue with bulkier substituents around the nitroxide did not generate the target molecule but demonstrated some of the interesting chemistry of the azaphenalene ring system

Porphyrin containing isoindoline nitroxides as potential fluorescence sensors of free radicals

A series of new spin-labeled porphyrin containing isoindoline nitroxide moieties were synthesized and characterized as potential free radical fluorescence sensors. Fluorescence-suppression was observed in the free-base monoradical porphyrins, whilst the free-base biradical porphyrins exhibited highly suppressed fluorescence about three times greater than the monoradical porphyrins. The observed fluorescence-suppression was attributed to enhanced intersystem crossing resulting from electronexchange between the doublet nitroxide and the excited porphyrin fluorophore. Notably, fluorescencesuppression was not as strong in the related metalated porphyrins, possibly due to insufficient spin coupling between the nitroxide and the porphyrin. Continuous wave EPR spectroscopy of the diradical porphyrins in fluid solution suggests that the nitroxyl-nitroxyl interspin distance is long enough and tumbling is fast enough not to detect dipolar coupling.

Edaravone containing isoindoline nitroxides for the potential treatment of cardiovascular ischaemia

A novel antioxidant for the potential treatment of ischaemia was designed by incorporating an isoindoline nitroxide into the framework of the free radical scavenger edaravone. 5-(3-Methyl-pyrazol-5-ol-1-yl)-1,1,3,3-tetramethylisoindolin-2-yloxyl 7 was prepared by N-arylation of 3-methyl-5-pyrazolone with 5-iodo-1,1,3,3-tetramethylisoindoline-2-yloxyl 8 in the presence of catalytic copper(I)iodide. Evaluation of 7, its methoxyamine derivative 10 and 5-carboxy-1,1,3,3-tetramethylisoindolin-2-yloxyl (CTMIO) against edaravone 1 in ischaemic rat atrial cardiomyocytes revealed significant decreases in cell death after prolonged ischaemia for each agent; however the protective effect of the novel antioxidant 7 (showing greater than 85% reduction in cell death at 100 μM) was significantly enhanced over that of edaravone 1 alone. Furthermore, the activity for 7 was found to be equal to or greater than the potent cardioprotective agent N6-cyclopentyladenosine (CPA). The methoxyamine adduct 10 and edaravone 1 showed no difference between the extent of reduction in cell death whilst CTMIO had only a modest protective effect.

Generation of profluorescent isoindoline nitroxides using click chemistry

Novel profluorescent nitroxides bearing a triazole linker between the coumarin fluorophore and an isoindoline nitroxide were prepared in good yields using the coppercatalyzed azide�alkyne 1,3-dipolar cycloaddition reaction (CuAAC). Nitroxides containing 7-hydroxy and 7-diethylamino substitution on their coumarin rings displayed significant fluorescence suppression, and upon reaction with methyl radicals, normal fluorescence emission was returned. The fluorescence emission for the 7-hydroxycoumarin nitroxide and its diamagnetic analogue was found to be strongly influenced by pH with maximal fluorescence emission achieved in basic solution. Solvent polarity was also shown to affect fluorescence emission. The significant difference in fluorescence output between the nitroxides and their corresponding diamagnetic analogues makes these compounds ideal tools for monitoring processes involving free-radical species.