La Boite The Story of an Australian Theatre Company

Since its genesis in 1925, La Boite has never been afraid of change. Despite controversies, crises and crippling set-backs that should have closed its stage doors many times, La Boite - which began life as the Brisbane Repertory Theatre Society - has proved itself an extraordinary survivor. When the opportunity came to build its own theatre, its inspired choice of theatre-in-the-round gave Brisbane an iconic performance space that attracted a whole new generation of actors, directors and designers and placed La Boite at the forefront of contemporary theatre practice. The place, in Katharine Brisbane’s words, “to see the red meat of theatre”. Always enterprising, with gritty determination it became a professional theatre company of national significance; and early in the new millennium triumphantly re-located to its new home at The Roundhouse Theatre. La Boite –The Story of an Australian Theatre Company both interrogates and celebrates the history of Queensland’s oldest theatre company. Highlighting the roles key people played in its evolution – particularly four remarkable women – Christine Comans explores La Boite’s colourful past, its cultural significance to Brisbane, and its vibrant and enduring role in the nation’s theatrical history.

Role of resting metabolic rate and energy expenditure in hunger and appetite control : a new formulation

A long-running issue in appetite research concerns the influence of energy expenditure on energy intake. More than 50 years ago, Otto G. Edholm proposed that "the differences between the intakes of food [of individuals] must originate in differences in the expenditure of energy". However, a relationship between energy expenditure and energy intake within any one day could not be found, although there was a correlation over 2 weeks. This issue was never resolved before interest in integrative biology was replaced by molecular biochemistry. Using a psychobiological approach, we have studied appetite control in an energy balance framework using a multi-level experimental system on a single cohort of overweight and obese human subjects. This has disclosed relationships between variables in the domains of body composition [fat-free mass (FFM), fat mass (FM)], metabolism, gastrointestinal hormones, hunger and energy intake. In this Commentary, we review our own and other data, and discuss a new formulation whereby appetite control and energy intake are regulated by energy expenditure. Specifically, we propose that FFM (the largest contributor to resting metabolic rate), but not body mass index or FM, is closely associated with self-determined meal size and daily energy intake. This formulation has implications for understanding weight regulation and the management of obesity.

A multiscale road map of cancer spheroids : incorporating experimental and mathematical modelling to understand cancer progression

Computational models represent a highly suitable framework, not only for testing biological hypotheses and generating new ones but also for optimising experimental strategies. As one surveys the literature devoted to cancer modelling, it is obvious that immense progress has been made in applying simulation techniques to the study of cancer biology, although the full impact has yet to be realised. For example, there are excellent models to describe cancer incidence rates or factors for early disease detection, but these predictions are unable to explain the functional and molecular changes that are associated with tumour progression. In addition, it is crucial that interactions between mechanical effects, and intracellular and intercellular signalling are incorporated in order to understand cancer growth, its interaction with the extracellular microenvironment and invasion of secondary sites. There is a compelling need to tailor new, physiologically relevant in silico models that are specialised for particular types of cancer, such as ovarian cancer owing to its unique route of metastasis, which are capable of investigating anti-cancer therapies, and generating both qualitative and quantitative predictions. This Commentary will focus on how computational simulation approaches can advance our understanding of ovarian cancer progression and treatment, in particular, with the help of multicellular cancer spheroids, and thus, can inform biological hypothesis and experimental design.

Systematic differences in membrane acyl composition associated with varying body mass in mammals occur in all phospholipid classes : an analysis of kidney and brain

The acyl composition of membrane phospholipids in kidney and brain of mammals of different body mass was examined. It was hypothesized that reduction in unsaturation index (number of double bonds per 100 acyl chains) of membrane phospholipids with increasing body mass in mammals would be made-up of similar changes in acyl composition across all phospholipid classes and that phospholipid class distribution would be regulated and similar in the same tissues of the different-sized mammals. The results of this study supported both hypotheses. Differences in membrane phospholipid acyl composition (i. e. decreased omega-3 fats, increased monounsaturated fats and decreased unsaturation index with increasing body size) were not restricted to any specific phospholipid molecule or to any specific phospholipid class but were observed in all phospholipid classes. With increase in body mass of mammals both monounsaturates and use of less unsaturated polyunsaturates increases at the expense of the long-chain highly unsaturated omega-3 and omega-6 polyunsaturates, producing decreases in membrane unsaturation. The distribution of membrane phospholipid classes was essentially the same in the different-sized mammals with phosphatidylcholine (PC) and phosphatidylethanolamine (PE) together constituting similar to 91% and similar to 88% of all phospholipids in kidney and brain, respectively. The lack of sphingomyelin in the mouse tissues and higher levels in larger mammals suggests an increased presence of membrane lipid rafts in larger mammals. The results of this study support the proposal that the physical properties of membranes are likely to be involved in changing metabolic rate.

Reversible transdifferentiation of blood vascular endothelial cells to a lymphatic-like phenotype in vitro

Blood vascular cells and lymphatic endothelial cells (BECs and LECs, respectively) form two separate vascular systems and are functionally distinct cell types or lineages with characteristic gene expression profiles. Interconversion between these cell types has not been reported. Here, we show that in conventional in vitro angiogenesis assays, human BECs of fetal or adult origin show altered gene expression that is indicative of transition to a lymphatic-like phenotype. This change occurs in BECs undergoing tubulogenesis in fibrin, collagen or Matrigel assays, but is independent of tube formation per se, because it is not inhibited by a metalloproteinase inhibitor that blocks tubulogenesis. It is also reversible, since cells removed from 3D tubules revert to a BEC expression profile upon monolayer culture. Induction of the lymphatic-like phenotype is partially inhibited by co-culture of HUVECs with perivascular cells. These data reveal an unexpected plasticity in endothelial phenotype, which is regulated by contact with the ECM environment and/or cues from supporting cells.

Terrestrial locomotion of the New Zealand short-tailed bat Mystacina tuberculata and the common vampire bat Desmodus rotundus

Bats (Chiroptera) are generally awkward crawlers, but the common vampire bat (Desmodus rotundus) and the New Zealand short-tailed bat (Mystacina tuberculata) have independently evolved the ability to manoeuvre well on the ground. In this study we describe the kinematics of locomotion in both species, and the kinetics of locomotion in M. tuberculata. We sought to determine whether these bats move terrestrially the way other quadrupeds do, or whether they possess altogether different patterns of movement on the ground than are observed in quadrupeds that do not fly. Using high-speed video analyses of bats moving on a treadmill, we observed that both species possess symmetrical lateral-sequence gaits similar to the kinematically defined walks of a broad range of tetrapods. At high speeds, D. rotundus use an asymmetrical bounding gait that appears to converge on the bounding gaits of small terrestrial mammals, but with the roles of the forelimbs and hindlimbs reversed. This gait was not performed by M. tuberculata. Many animals that possess a single kinematic gait shift with increasing speed from a kinetic walk (where kinetic and potential energy of the centre of mass oscillate out of phase from each other) to a kinetic run (where they oscillate in phase). To determine whether the single kinematic gait of M. tuberculata meets the kinetic definition of a walk, a run, or a gait that functions as a walk at low speed and a run at high speed, we used force plates and high-speed video recordings to characterize the energetics of the centre of mass in that species. Although oscillations in kinetic and potential energy were of similar magnitudes, M. tuberculata did not use pendulum-like exchanges of energy between them to the extent that many other quadrupedal animals do, and did not transition from a kinetic walk to kinetic run with increasing speed. The gait of M. tuberculata is kinematically a walk, but kinetically run-like at all speeds.

Acoustic identification of 12 species of echolocating bat by discriminant function analysis and artificial neural networks

We recorded echolocation calls from 14 sympatric species of bat in Britain. Once digitised, one temporal and four spectral features were measured from each call. The frequency-time course of each call was approximated by fitting eight mathematical functions, and the goodness of fit, represented by the mean-squared error, was calculated. Measurements were taken using an automated process that extracted a single call from background noise and measured all variables without intervention. Two species of Rhinolophus were easily identified from call duration and spectral measurements. For the remaining 12 species, discriminant function analysis and multilayer back-propagation perceptrons were used to classify calls to species level. Analyses were carried out with and without the inclusion of curve-fitting data to evaluate its usefulness in distinguishing among species. Discriminant function analysis achieved an overall correct classification rate of 79% with curve-fitting data included, while an artificial neural network achieved 87%. The removal of curve-fitting data improved the performance of the discriminant function analysis by 2 %, while the performance of a perceptron decreased by 2 %. However, an increase in correct identification rates when curve-fitting information was included was not found for all species. The use of a hierarchical classification system, whereby calls were first classified to genus level and then to species level, had little effect on correct classification rates by discriminant function analysis but did improve rates achieved by perceptrons. This is the first published study to use artificial neural networks to classify the echolocation calls of bats to species level. Our findings are discussed in terms of recent advances in recording and analysis technologies, and are related to factors causing convergence and divergence of echolocation call design in bats.

Acoustic identification of twelve species of echolocating bat by discriminant function analysis and artificial neural networks

We recorded echolocation calls from 14 sympatric species of bat in Britain. Once digitised, one temporal and four spectral features were measured from each call. The frequency-time course of each call was approximated by fitting eight mathematical functions, and the goodness of fit, represented by the mean-squared error, was calculated. Measurements were taken using an automated process that extracted a single call from background noise and measured all variables without intervention. Two species of Rhinolophus were easily identified from call duration and spectral measurements. For the remaining 12 species, discriminant function analysis and multilayer back-propagation perceptrons were used to classify calls to species level. Analyses were carried out with and without the inclusion of curve-fitting data to evaluate its usefulness in distinguishing among species. Discriminant function analysis achieved an overall correct classification rate of 79% with curve-fitting data included, while an artificial neural network achieved 87%. The removal of curve-fitting data improved the performance of the discriminant function analysis by 2 %, while the performance of a perceptron decreased by 2 %. However, an increase in correct identification rates when curve-fitting information was included was not found for all species. The use of a hierarchical classification system, whereby calls were first classified to genus level and then to species level, had little effect on correct classification rates by discriminant function analysis but did improve rates achieved by perceptrons. This is the first published study to use artificial neural networks to classify the echolocation calls of bats to species level. Our findings are discussed in terms of recent advances in recording and analysis technologies, and are related to factors causing convergence and divergence of echolocation call design in bats.

Awakening the spirit : telling the stories

Stephen Page talking with Cheryl Stock Stephen Page is one of the most significant dance artists working in Australia today, unique in his ability to forge and sustain a company of Indigenous artists through his seminal leadership of Bangarra Dance Theatre, which celebrated its 20 year anniversary in 2009. Together with the many artists who have contributed to the Bangarra vision, Stephen has created a distinctive contemporary Indigenous dance style and approach, celebrated for the stories it tells of the Aboriginal and Torres Strait Islander experience. Fusing the traditional with the contemporary through a connection to the spirit of the land and its people, Stephen has inspired and influenced a generation of Aboriginal and Torres Strait Islander dance and theatre artists as a choreographer, director and mentor. His down to earth humour, his passion and his sensitivity draw us as audience, Indigenous and non-Indigenous alike, to his theatrical stories of place and spirit – both ancient and modern – in ways that simultaneously transcend and reaffirm the particular cultural experience which informs them. This conversation covers the early years of growing up with his 'urban clan', discovering dance and politics and his spiritual awakening at Yirrkala. Stephen then describes moving in and out of different realities as a member of Sydney Dance Company whilst simultaneously exploring his Indigenous dance voice, the transition from dancer to choreographer, creating the Bangarra identity and the intercultural experiment of 'Rites' with the Australian Ballet. The last section looks at his various roles as an artistic director and nurturing the next generation of Indigenous artists.

Flightless, secreted through a late endosome/lysosome pathway, binds LPS and dampens cytokine secretion.

Flightless (Flii) is upregulated in response to wounding and has been shown to function in wound closure and scarring. In macrophages intracellular Flii negatively modulates TLR signalling and dampens cytokine production. We now show that Flii is constitutively secreted from macrophages and fibroblasts and is present in human plasma. Secretion from fibroblasts is upregulated in response to scratch wounding and LPS-activated macrophages also temporally upregulate their secretion of Flii. Using siRNA, wild-type and mutant proteins we show that Flii is secreted via a late endosomal/lysosomal pathway that is regulated by Rab7 and Stx11. Flii contains 11 leucine rich repeat (LRR) domains in its N-terminus that have nearly 50% similarity to those in the extracellular pathogen binding portion of Toll-like receptor 4 (TLR4). We show secreted Flii can also bind LPS and has the ability to alter macrophage activation. LPS activation of macrophages in Flii depleted conditioned media leads to enhanced macrophage activation and increased TNF secretion compared to cells activated in the presence of Flii. These results show secreted Flii binds to LPS and in doing so alters macrophage activation and cytokine secretion, suggesting that like the intracellular pool of Flii, secreted Flii also has the ability to alter inflammation.

Increased plant volatile production affects oviposition, but not larval development, in the moth Helicoverpa armigera

It is well established that herbivorous insects respond to changes in plant odour production, but little attention has been given to whether these responses relate to direct fitness costs of plant volatile production on insect growth and survival. Here, we use transgenic Nicotiana tabacum (tobacco) plants that produce relatively large amounts of the volatile (S)-linalool to study whether the responses of egg-laying herbivorous insects to linalool production relate directly to the growth and survival of offspring. In choice tests, fewer eggs were laid on transgenic plants compared with non-transformed controls, indicating that increased linalool emissions have a deterrent effect on Helicoverpa armigera oviposition. Larval survival and larval mass after feeding on transgenic leaves, however, was comparable to non-transformed controls. (S)-linalool, whether in volatile or sequestered form, does not appear to have a direct effect on offspring fitness in this moth. We discuss how the ecology of this polyphagous moth species may necessitate a high tolerance for certain volatiles and their related non-volatile compounds, and suggest that responses by adult female H. armigera moths towards increased linalool production may be context specific and relate to other indirect effects on fitness.

Differences in membrane acyl phospholipid composition between an endothermic mammal and an ectothermic reptile are not limited to any phospholipid class

This study examined questions concerning differences in the acyl composition of membrane phospholipids that have been linked to the faster rates of metabolic processes in endotherms versus ectotherms. In liver, kidney, heart and brain of the ectothermic reptile, Trachydosaurus rugosus, and the endothermic mammal, Rattus norvegicus, previous findings of fewer unsaturates but a greater unsaturation index (UI) in membranes of the mammal versus those of the reptile were confirmed. Moreover, the study showed that the distribution of phospholipid head-group classes was similar in the same tissues of the reptile and mammal and that the differences in acyl composition were present in all phospholipid classes analysed, suggesting a role for the physical over the chemical properties of membranes in determining the faster rates of metabolic processes in endotherms. The most common phosphatidylcholine (PC) molecules present in all tissues (except brain) of the reptile were 16:0/18:1, 16:0/18:2, 18:0/18:2, 18:1/18:1 and 18:1/18:2, whereas arachidonic acid (20:4), containing PCs 16:0/ 20: 4, 18: 0/ 20: 4, were the common molecules in the mammal. The most abundant phosphatidylethanolamines ( PE) used in the tissue of the reptile were 18:0/18:2, 18:0/20:4, 18:1/18:1, 18:1/18:2 and 18:1/20:4, compared to 16: 0/ 18: 2, 16: 0/ 20: 4, 16: 0/ 22: 6, 18: 0/ 20: 4, 18: 0/ 22: 6 and 18:1/20: 4 in the mammal. UI differences were primarily due to arachidonic acid found in both PC and PEs, whereas docosahexaenoic acid (22:6) was a lesser contributor mainly within PEs and essentially absent in the kidney. The phospholipid composition of brain was more similar in the reptile and mammal compared to those of other tissues.

KRAB zinc-finger proteins localise to novel KAP1-containing foci that are adjacent to PML nuclear bodies

The KRAB-zinc finger proteins (KRAB-ZFPs) represent a very large, but poorly understood, family of transcriptional regulators in mammals. They are thought to repress transcription via their interaction with KRAB-associated protein 1 (KAP1), which then assembles a complex of chromatin modifiers to lay down histone marks that are associated with inactive chromatin. Studies of KRAB-ZFP/KAP1-mediated gene silencing, using reporter constructs and ectopically expressed proteins, have shown colocalisation of both KAP1 and repressed reporter target genes to domains of constitutive heterochromatin in the nucleus. However, we show here that although KAP1 does indeed become recruited to pericentric heterochromatin during differentiation of mouse embryonic stem (ES) cells, endogenous KRAB-ZFPs do not. Rather, KRAB-ZFPs and KAP1 relocalise to novel nucleoplasmic foci that we have termed KRAB- and KAP1-associated (KAKA) foci. HP1s can also concentrate in these foci and there is a close spatial relationship between KAKA nuclear foci and PML nuclear bodies. Finally, we reveal differential requirements for the recruitment of KAP1 to pericentric heterochromatin and KAKA foci, and suggest that KAKA foci may contain sumoylated KAP1 - the form of the protein that is active in transcriptional repression.

Mechanical filtering for narrow-band hearing in the weta

This paper constitutes a major attempt to associate tympanic deflections with the mechanoreceptor organ location in an acoustic insect. The New Zealand tree weta (Hemideina thoracica) has tympanal ears located on each of the prothoracic tibiae. The tympana exhibit a sclerotized oval plate, membranous processes bulging out from the tibial cuticle and many loosely suspended ripples. We used microscanning laser Doppler vibrometry to determine how such a tympanal membrane vibrates in response to sound and whether the sclerotized region plays a role in hearing. The tympanum displays a single resonance at the calling frequency of the male, an unusual example of an insect tympana acting as a narrow bandpass filter. Both tympana resonate in phase with the stimulus and with each other. Histological sections show that the tympanal area is divided into two distinct regions, as in other ensiferans. An oval plate lies in the middle of a thickened region and is surrounded by a transparent and uniformly thin region. It is hinged dorsally to the tympanal rim and thus resembles the model of a ‘hinged flap’. The thickened region appears to act as a damping mass on the oscillation of the thin region, and vibration displacement is reduced in this area. The thinner area vibrates with higher amplitude, inducing mechanical pressure on the dorsal area adjacent to the crista acustica. We present a new model showing how the thickened region might confer a mechanical gain onto the activation of the crista acustica sensory neurons during the sound-induced oscillations.