Staurosporine augments EGF-mediated EMT in PMC42-LA cells through actin depolymerisation, focal contact size reduction and Snail1 induction : a model for cross-modulation

Background A feature of epithelial to mesenchymal transition (EMT) relevant to tumour dissemination is the reorganization of actin cytoskeleton/focal contacts, influencing cellular ECM adherence and motility. This is coupled with the transcriptional repression of E-cadherin, often mediated by Snail1, Snail2 and Zeb1/δEF1. These genes, overexpressed in breast carcinomas, are known targets of growth factor-initiated pathways, however it is less clear how alterations in ECM attachment cross-modulate to regulate these pathways. EGF induces EMT in the breast cancer cell line PMC42-LA and the kinase inhibitor staurosporine (ST) induces EMT in embryonic neural epithelial cells, with F-actin de-bundling and disruption of cell-cell adhesion, via inhibition of aPKC. Methods PMC42-LA cells were treated for 72 h with 10 ng/ml EGF, 40 nM ST, or both, and assessed for expression of E-cadherin repressor genes (Snail1, Snail2, Zeb1/δEF1) and EMT-related genes by QRT-PCR, multiplex tandem PCR (MT-PCR) and immunofluorescence +/- cycloheximide. Actin and focal contacts (paxillin) were visualized by confocal microscopy. A public database of human breast cancers was assessed for expression of Snail1 and Snail2 in relation to outcome. Results When PMC42-LA were treated with EGF, Snail2 was the principal E-cadherin repressor induced. With ST or ST+EGF this shifted to Snail1, with more extreme EMT and Zeb1/δEF1 induction seen with ST+EGF. ST reduced stress fibres and focal contact size rapidly and independently of gene transcription. Gene expression analysis by MT-PCR indicated that ST repressed many genes which were induced by EGF (EGFR, CAV1, CTGF, CYR61, CD44, S100A4) and induced genes which alter the actin cytoskeleton (NLF1, NLF2, EPHB4). Examination of the public database of breast cancers revealed tumours exhibiting higher Snail1 expression have an increased risk of disease-recurrence. This was not seen for Snail2, and Zeb1/δEF1 showed a reverse correlation with lower expression values being predictive of increased risk. Conclusion ST in combination with EGF directed a greater EMT via actin depolymerisation and focal contact size reduction, resulting in a loosening of cell-ECM attachment along with Snail1-Zeb1/δEF1 induction. This appeared fundamentally different to the EGF-induced EMT, highlighting the multiple pathways which can regulate EMT. Our findings add support for a functional role for Snail1 in invasive breast cancer.

Sphingolipid distribution changes with age in the human lens

The formation of an internal barrier to the diffusion of small molecules in the lens during middle age is hypothesized to be a key event in the development of age-related nuclear (ARN) cataract. Changes in membrane lipids with age may be responsible. In this study, we investigated the effect of age on the distribution of sphingomyelins, the most abundant lens phospholipids. Human lens sections were initially analyzed by MALDI mass spectrometry imaging. A distinct annular distribution of the dihydrosphingomyelin, DHSM (d18:0/16:0), in the barrier region was observed in 64- and 70-year-old lenses but not in a 23-year-old lens. An increase in the dihydroceramide, DHCer (d18:0/16:0), in the lens nucleus was also observed in the older lenses. These findings were supported by ESI mass spectrometry analysis of lipid extracts from lenses dissected into outer, barrier, and nuclear regions. A subsequent analysis of 18 lenses ages 20-72 years revealed that sphingomyelin levels increased with age in the barrier region until reaching a plateau at approximately 40 years of age. Such changes in lipid composition will have a significant impact on the physical properties of the fiber cell membranes and may be associated with the formation of a barrier.-Deeley, J. M., J. A. Hankin, M. G. Friedrich, R. C. Murphy, R. J. W. Truscott, T. W. Mitchell, and S. J. Blanksby. Sphingolipid distribution changes with age in the human lens. J. Lipid Res. 2010. 51: 2753-2760.

Human lens lipids differ markedly from those of commonly used experimental animals

Electrospray ionisation tandem mass spectrometry has allowed the unambiguous identification and quantification of individual lens phospholipids in human and six animal models. Using this approach ca. 100 unique phospholipids have been characterised. Parallel analysis of the same lens extracts by a novel direct-insertion electron-ionization technique found the cholesterol content of human lenses to be significantly higher (ca. 6 times) than lenses from the other animals. The most abundant phospholipids in all the lenses examined were choline-containing phospholipids. In rat, mouse, sheep, cow, pig and chicken, these were present largely as phosphatidylcholines, in contrast 66% of the total phospholipid in Homo sapiens was sphingomyelin, with the most abundant being dihydrosphingomyelins, in particular SM(d18:0/16:0) and SM(d18:0/24:1). The abundant glycerophospholipids within human lenses were found to be predominantly phosphatidylethanolamines and phosphatidylserines with surprisingly high concentrations of ether-linked alkyl chains identified in both classes. This study is the first to identify the phospholipid class (head-group) and assign the constituent fatty acid(s) for each lipid molecule and to quantify individual lens phospholipids using internal standards. These data clearly indicate marked differences in the membrane lipid composition of the human lens compared to commonly used animal models and thus predict a significant variation in the membrane properties of human lens fibre cells compared to those of other animals. © 2008 Elsevier B.V. All rights reserved.

Contact with existing adipose tissue is inductive for adipogenesis in matrigel

The effect of adipose tissue on inductive adipogenesis within Matrigel (BD Biosciences) was assessed by using a murine chamber model containing a vascular pedicle. Three-chamber configurations that varied in the access to an adipose tissue source were used, including sealed- and open-chamber groups that had no access and limited access, respectively, to the surrounding adipose tissue, and a sealed-chamber group in which adipose tissue was placed as an autograft. All groups showed neovascularization, but varied in the amount of adipogenesis seen in direct relation to their access to preexisting adipose tissue: open chambers showed strong adipogenesis, whereas the sealed chambers had little or no adipose tissue; adipogenesis was restored in the autograft chamber group that contained 2- to 5-mg fat autografts. These showed significantly more adipogenesis than the sealed chambers with no autograft (p < 0.01). Autografts with 1 mg of fat were capable of producing adipogenesis but did so less consistently than the larger autografts. These findings have important implications for adipose tissue engineering strategies and for understanding de novo production of adipose tissue.

Hydrodynamic theory of liquid slippage on a solid substrate near a moving contact line

In this Letter a hydrodynamic theory of liquid slippage on a solid substrate near a moving contact line is proposed. A family of spatially varying slip lengths in the Navier slip law recovers the results of past formulations for slip in continuum theories and molecular dynamics simulations and is consistent with well-established experimental observations of complete wetting. This formulation gives a general approach for continuum hydrodynamic theories. New fluid flow behaviors are also predicted yet to be seen in experiment. © 2013 American Physical Society.

Examining early childhood education through the lens of education for sustainability : revisioning rights

This chapter calls for rethinking about the rights base of early childhood education. The United Nations Convention on the Rights of the Child (UNCRC) (UNICEF1989) has been seen as an important foundation internationally for early childhood education practise. In this paper, I argue that whilst the UNCRC (1989) still serves its aspirational purpose, it is an inadequate vehicle for enacting early childhood education in the twenty-first century given the pressing challenges of sustainability. The UNCRC emerged from an individual rights perspective, and despite attempts to broaden the rights agenda towards greater child participation and engagement, these approaches offer an inadequate response to global sustainability concerns. In this chapter, I propose a five dimensional approach to rights that acknowledges the fundamental rights of children as espoused in the UNCRC and the call for agentic rights as advocated more recently by early childhood academics and practitioners. Additionally, however, discussion of collective rights, intergenerational rights and bio/ecocentic rights are forwarded, offering a expanded way to think about rights with implications for how early childhood education is practised and researched.

Measurement of contact voltage drop and resistance in organic solar cells

Bulk heterojunction organic solar cells based on poly[4,7-bis(3- dodecylthiophene-2-yl) benzothiadiazole-co-benzothiadiazole] and [6,6]-phenyl C71-butyric acid methyl ester are investigated. A prominent kink is observed in the fourth quadrant of the current density-voltage (J-V) response. Annealing the active layer prior to cathode deposition eliminates the kink. The kink is attributed to an extraction barrier. The J-V response in these devices is well described by a power law. This behavior is attributed to an imbalance in charge carrier mobility. An expected photocurrent for the device displaying a kink in the J-V response is determined by fitting to a power law. The difference between the expected and measured photocurrent allows for the determination of a voltage drop within the device. Under simulated 1 sun irradiance, the peak voltage drop and contact resistance at short circuit are 0.14 V and 90 Ω, respectively. © 2012 American Institute of Physics.

Epistemological lens : birth, death and ecology of documentary practices

This paper considers the epistemological life cycle of the camera lens in documentary practices. The 19th century industrial economies that manufactured and commercialised the camera lens have engendered political and economic contingencies on documentary practices to sustain a hegemonic and singular interpretive epistemology. Colonial documentary practices are considered from the viewpoint of manipulative hegemonic practices - all of which use the interpretive epistemology of the camera lens to capitalise a viewpoint which is singular and possesses the power to sustain its own status and economic privilege. I suggest that decolonising documentary practices can be nurtured in what Boaventura de Sousa Santos proposes as an 'ecology of knowledges' (Andreotti, Ahenakew, & Cooper 2011) - a way of including the epistemologies of cultures beyond the 'abyssal' (Santos), outside the limits of epistemological dominance. If an 'epistemicide' (Santos) of indigenous knowledges in the dominant limits has occurred then in an ecology of knowledges the limits become limitless and what were once invisible knowledges, come into their own ontological and epistemological being: as free agents and on their own terms. In an ecology of knowledges, ignorance and blindness may still exist but are not privileged. The decolonisation of documentary practices inevitably destabilises prevailing historicities and initiates ways for equal privilege to exist between multiple epistemologies.

Paternal postnatal depressive symptoms, infant sleeping and feeding behaviors, and rigid parental regulation : a correlational study

Paternal postnatal depression (PND) is now recognized as a serious and prevalent problem, associated with poorer well-being and functioning of all family members. Aspects of infant temperament, sleeping and feeding perceived by parents as problematic are associated with maternal PND, however, less is known about paternal PND. This study investigated depressive symptoms (Edinburgh postnatal depression scale (EPDS)) in 219 fathers of infants aged from 1 to 24 weeks (median 7.0 weeks). Infant predictor variables were sleeping problems, feeding problems and both mother and father reported temperament. Control variables were partner’s support, other support and life events. Rigidity of parenting beliefs regarding infant regulation was also measured as a potential moderating factor. Infant feeding difficulties were associated with paternal depressive symptoms, subsuming the variance associated with both sleep problems and temperament. This relationship was not moderated by regulation beliefs. It was concluded that infant feeding is important to fathers. Fathers of infants with feeding difficulties may not be able to fulfill their idealized construction of involved fatherhood. Role incongruence may have an etiological role in paternal PND.

The influence of injury cause, contact-sport participation, and personal knowledge on expectation of outcome from mild traumatic brain injury

Objective: This study investigated the influence of injury cause, contact-sport participation, and prior knowledge of mild traumatic brain injury (mTBI) on injury beliefs and chronic symptom expectations of mTBI. Method: A total of 185 non-contact-sport players (non-CSPs) and 59 contact-sport players (CSPs) with no history of mTBI were randomly allocated to one of two conditions in which they read either a vignette depicting a sport-related mTBI (mTBIsport) or a motor-vehicle-accident-related mTBI (mTBIMVA). The vignettes were otherwise standardized to convey the same injury parameters (e.g., duration of loss of consciousness). After reading a vignette, participants reported their injury beliefs (i.e., perceptions of injury undesirability, chronicity, and consequences) and their expectations of chronic postconcussion syndrome (PCS) and posttraumatic stress disorder (PTSD) symptoms. Results: Non-CSPs held significantly more negative beliefs and expected greater PTSD symptomatology and greater PCS affective symptomatology from an mTBIMVA vignette thann mTBIsport vignette, but this difference was not found for CSPs. Unlike CSPs, non-CSPs who personally knew someone who had sustained an mTBI expected significantly less PCS symptomatology than those who did not. Despite these different results for non-CSPs and CSPs, overall, contact-sport participation did not significantly affect injury beliefs and symptom expectations from an mTBIsport. Conclusions: Expectations of persistent problems after an mTBI are influenced by factors such as injury cause even when injury parameters are held constant. Personal knowledge of mTBI, but not contact sport participation, may account for some variability in mTBI beliefs and expectations. These factors require consideration when assessing mTBI outcome.

SBS’s First Contact is the real ‘festering sore’ of the nation

The SBS/Blackfella Films production First Contact – that takes six non-Indigenous people and immerses them into Aboriginal Australia for the first time – captured the nation’s attention this week amassing a television audience nearing 1 million viewers, while the program’s Twitter hashtag #FirstContactSBS trended worldwide. Over the three episodes, we saw the participants get their “first contact” with Aboriginal Australia as they were welcomed into the homes of Aboriginal people in the city and in the bush...

Locally weighted learning methods for non-rigid robot control

This thesis develops a novel approach to robot control that learns to account for a robot's dynamic complexities while executing various control tasks using inspiration from biological sensorimotor control and machine learning. A robot that can learn its own control system can account for complex situations and adapt to changes in control conditions to maximise its performance and reliability in the real world. This research has developed two novel learning methods, with the aim of solving issues with learning control of non-rigid robots that incorporate additional dynamic complexities. The new learning control system was evaluated on a real three degree-of-freedom elastic joint robot arm with a number of experiments: initially validating the learning method and testing its ability to generalise to new tasks, then evaluating the system during a learning control task requiring continuous online model adaptation.

The scholarship of Jonathan Silin: a reading through the lens of sexuality

While Jonathan Silin's ideas have challenged early childhood educators to think seriously about the relationship between developmentalism and revisioning early education, they have done much more than this. They also challenge us to know who we are and how our identities might be enacted in our teacher-selves, whether in the classroom with young children, teacher education students or engaging professionally with teachers. In doing so he shows how to resist injustice and unmasks ways in which institutions function in society to marginalise and exclude.

A call for better care: the impact of postnatal contact services on women’s parenting confidence and experiences of postpartum care in Queensland, Australia

Background Universal postnatal contact services are provided in several Australian states, but their impact on women’s postnatal care experience has not been evaluated. Furthermore, there is lack of evidence or consensus about the optimal type and amount of postpartum care after hospital discharge for maternal outcomes. This study aimed to assess the impact of providing Universal Postnatal Contact Service (UPNCS) funding to public birthing facilities in Queensland, Australia on women’s postnatal care experiences, and associations between amount and type (telephone or home visits) of contact on parenting confidence, and perceived sufficiency and quality of postnatal care. Methods Data collected via retrospective survey of postnatal women (N = 3,724) were used to compare women who birthed in UPNCS-funded and non-UPNCS-funded facilities on parenting confidence, sufficiency of postnatal care, and perceived quality of postnatal care. Associations between receiving telephone and home visits and the same outcomes, regardless of UPNCS funding, were also assessed. Results Women who birthed in an UPNCS-funded facility were more likely to receive postnatal contact, but UPNCS funding was not associated with parenting confidence, or perceived sufficiency or perceived quality of care. Telephone contact was not associated with parenting confidence but had a positive dose–response association with perceived sufficiency and quality. Home visits were negatively associated with parenting confidence when 3 or more were received, had a positive dose–response association with perceived sufficiency and were positively associated with perceived quality when at least 6 were received. Conclusions Funding for UPNCS is unlikely to improve population levels of maternal parenting confidence, perceived sufficiency or quality of postpartum care. Where only minimal contact can be provided, telephone may be more effective than home visits for improving women’s perceived sufficiency and quality of care. Additional service initiatives may be needed to improve women’s parenting confidence.