Direct repression of MYB by ZEB1 suppresses proliferation and epithelial gene expression during epithelial-to-mesenchymal transition of breast cancer cells

Introduction Epithelial-to-mesenchymal transition (EMT) promotes cell migration and is important in metastasis. Cellular proliferation is often downregulated during EMT, and the reverse transition (MET) in metastases appears to be required for restoration of proliferation in secondary tumors. We studied the interplay between EMT and proliferation control by MYB in breast cancer cells. Methods MYB, ZEB1, and CDH1 expression levels were manipulated by lentiviral small-hairpin RNA (shRNA)-mediated knockdown/overexpression, and verified with Western blotting, immunocytochemistry, and qRT-PCR. Proliferation was assessed with bromodeoxyuridine pulse labeling and flow cytometry, and sulforhodamine B assays. EMT was induced with epidermal growth factor for 9 days or by exposure to hypoxia (1% oxygen) for up to 5 days, and assessed with qRT-PCR, cell morphology, and colony morphology. Protein expression in human breast cancers was assessed with immunohistochemistry. ZEB1-MYB promoter binding and repression were determined with Chromatin Immunoprecipitation Assay and a luciferase reporter assay, respectively. Student paired t tests, Mann–Whitney, and repeated measures two-way ANOVA tests determined statistical significance (P < 0.05). Results Parental PMC42-ET cells displayed higher expression of ZEB1 and lower expression of MYB than did the PMC42-LA epithelial variant. Knockdown of ZEB1 in PMC42-ET and MDA-MB-231 cells caused increased expression of MYB and a transition to a more epithelial phenotype, which in PMC42-ET cells was coupled with increased proliferation. Indeed, we observed an inverse relation between MYB and ZEB1 expression in two in vitro EMT cell models, in matched human breast tumors and lymph node metastases, and in human breast cancer cell lines. Knockdown of MYB in PMC42-LA cells (MYBsh-LA) led to morphologic changes and protein expression consistent with an EMT. ZEB1 expression was raised in MYBsh-LA cells and significantly repressed in MYB-overexpressing MDA-MB-231 cells, which also showed reduced random migration and a shift from mesenchymal to epithelial colony morphology in two dimensional monolayer cultures. Finally, we detected binding of ZEB1 to MYB promoter in PMC42-ET cells, and ZEB1 overexpression repressed MYB promoter activity. Conclusions This work identifies ZEB1 as a transcriptional repressor of MYB and suggests a reciprocal MYB-ZEB1 repressive relation, providing a mechanism through which proliferation and the epithelial phenotype may be coordinately modulated in breast cancer cells.

Knowledge ecosystems of early career academics : a grounded theory of experiencing information use for learning in developmental networks

This study explored early career academics' experiences in using information to learn while building their networks for professional development. A 'knowledge ecosystem' model was developed consisting of informal learning interactions such as relating to information to create knowledge and engaging in mutually supportive relationships. Findings from this study present an alternative interpretation of information use for learning that is focused on processes manifesting as human interactions with informing entities revolving around the contexts of reciprocal human relationships.

On secure multi-party computation in black-box groups

We study the natural problem of secure n-party computation (in the passive, computationally unbounded attack model) of the n-product function f G (x 1,...,x n ) = x 1 ·x 2 ⋯ x n in an arbitrary finite group (G,·), where the input of party P i is x i  ∈ G for i = 1,...,n. For flexibility, we are interested in protocols for f G which require only black-box access to the group G (i.e. the only computations performed by players in the protocol are a group operation, a group inverse, or sampling a uniformly random group element). Our results are as follows. First, on the negative side, we show that if (G,·) is non-abelian and n ≥ 4, then no ⌈n/2⌉-private protocol for computing f G exists. Second, on the positive side, we initiate an approach for construction of black-box protocols for f G based on k-of-k threshold secret sharing schemes, which are efficiently implementable over any black-box group G. We reduce the problem of constructing such protocols to a combinatorial colouring problem in planar graphs. We then give two constructions for such graph colourings. Our first colouring construction gives a protocol with optimal collusion resistance t < n/2, but has exponential communication complexity O(n*2t+1^2/t) group elements (this construction easily extends to general adversary structures). Our second probabilistic colouring construction gives a protocol with (close to optimal) collusion resistance t < n/μ for a graph-related constant μ ≤ 2.948, and has efficient communication complexity O(n*t^2) group elements. Furthermore, we believe that our results can be improved by further study of the associated combinatorial problems.

Enhancing social work interprofessional learning through across university and industry collaboration : early steps in the Advanced Health Directives Project

There is ongoing interest in strategies for enhancing the reciprocal benefit derived from social work placements by students, host agencies, and universities. There is also recognition that interprofessional learning is an important aspect of social work education,and that field education placements have a role to play in this learning. This article reports on an innovation in community-engaged learning undertaken between a major public hospital and a university, where a team of social work and law students contributed to a focused inquiry into a socio-legal practice challenge faced by the hospital, namely the use of Advanced Health Directives (AHDs).Various collaborative processes involved in the early phase of the AHD project are reflected on by participants.A preliminary evaluation supports the value of taking a systematic approach to university–industry engagement where interprofessional collaboration occurs vertically and horizontally within and across university and placement hosting agencies.

Hydrolysis of genotoxic methyl-substituted oxiranes : Experimental kinetic and semiempirical studies

The kinetics of acid-catalyzed hydrolysis of seven methylated aliphatic epoxides - R1R2C(O)CR3R4 (A: R1=R2=R3=R4=H; B: R1=R2=R3=H, R4=Me; C: R1=R2=H, R3=R4=Me; D: R1=R3=H, R2=R4=Me(trans); E: R1=R3=H, R2=R4=Me(cis); F: R1=R3=R4=Me, R2=H; G: R1=R2=R3=R4=Me) - has been studied at 36 ± 1.5°C. Compounds with two methyl groups at the same carbon atom of the oxirane ring exhibit highest rate constants (k(eff) in reciprocal molar concentration per second: 11.0 ± 1.3 for C, 10.7 ± 2.1 for F, and 8.7 ± 0.7 for G as opposed to 0.124 ± 0.003 for B, 0.305 ± 0.003 for D, and 0.635 ± 0.036 for E). Ethylene oxide (A) displays the lowest rate of hydrolysis (0.027 M-1 s-1). The results are consistent with literature data available for compounds A, B, and C. To model the reactivities we have employed quantum chemical calculations (MNDO, AM1, PM3, and MINDO/3) of the main reaction species. There is a correlation of the logarithm k(eff) with the total energy of epoxide ring opening. The best correlation coefficients (r) were obtained using the AM1 and MNDO methods (0.966 and 0.957, respectively). However, unlike MNDO, AM1 predicts approximately zero energy barriers for the oxirane ring opening of compounds B, C, E and G, which is not consistent with published kinetic data. Thus, the MNDO method provides a preferential means of modeling the acidic hydrolysis of the series of methylated oxiranes. The general ranking of mutagenicity in vitro, A > B > C, is in line with the concept that this sequence also gradually leaves the expoxide reactivity optimal for genotoxicity toward reactivities leading to higher biological detoxifications.

Nearness and revealing : The edible veil of the sensible being.

Taking cues from the fragility and grace enfolded within Asian cuisine, this paper explores recent experimentation of an edible rice paper veil. The veil fashions a 'secondary skin', what Jeffery Schnapp the author of 'The Fabric of Modern Times', calls an "object for prosthetic shelf extension...bearing a uniquely intimate and direct relation to the human body" (Schnapp, 1997:197). The process reveals a layered material mutable to moisture and humidity, changing its elastic state in relation to body and surroundings. The moving, breathing, sweating surface of the body further modifies both veil and bodily experience drawing forth deeper emotional responses. The implications here offer a reciprocal affect, a revealing, where new materiality evokes the threshold to a new sensible being, one aware of the depth of material consciousness and inter-corporeal engagement, and which extends the relations between thinking and being of Heidegger and Shklovsky's seminal works.

Do not-for-profits need their own conceptual framework?

This paper raises the issue of whether not-for-profit (NFP) organisations require a conceptual framework that acknowledges their mission imperative and enables them to discharge their broader accountability. Relying on publicly available documentation and literature, it suggests that current conceptaul Frameworks for the for-profit and public sectors are inadequate in meeting the accountability needs of broader NFP-specific accountability and the formulation of NFP-appropriate reporting practice, including the provision of financial and non-financial reporting. The paper thus theoretically challenges existing financial reporting arrangements and investes debate on their future direction.

On-line estimation of Allan variance parameters

A new online method is presented for estimation of the angular random walk and rate random walk coefficients of IMU (inertial measurement unit) gyros and accelerometers. The online method proposes a state space model and proposes parameter estimators for quantities previously measured from off-line data techniques such as the Allan variance graph. Allan variance graphs have large off-line computational effort and data storage requirements. The technique proposed here requires no data storage and computational effort of O(100) calculations per data sample.

Anomaly detection in online social networks : using data-mining techniques and fuzzy logic

This research is a step forward in improving the accuracy of detecting anomaly in a data graph representing connectivity between people in an online social network. The proposed hybrid methods are based on fuzzy machine learning techniques utilising different types of structural input features. The methods are presented within a multi-layered framework which provides the full requirements needed for finding anomalies in data graphs generated from online social networks, including data modelling and analysis, labelling, and evaluation.

A transcriptome resource for the koala (Phascolarctos cinereus) : insights into koala retrovirus transcription and sequence diversity

Background The koala, Phascolarctos cinereus, is a biologically unique and evolutionarily distinct Australian arboreal marsupial. The goal of this study was to sequence the transcriptome from several tissues of two geographically separate koalas, and to create the first comprehensive catalog of annotated transcripts for this species, enabling detailed analysis of the unique attributes of this threatened native marsupial, including infection by the koala retrovirus. Results RNA-Seq data was generated from a range of tissues from one male and one female koala and assembled de novo into transcripts using Velvet-Oases. Transcript abundance in each tissue was estimated. Transcripts were searched for likely protein-coding regions and a non-redundant set of 117,563 putative protein sequences was produced. In similarity searches there were 84,907 (72%) sequences that aligned to at least one sequence in the NCBI nr protein database. The best alignments were to sequences from other marsupials. After applying a reciprocal best hit requirement of koala sequences to those from tammar wallaby, Tasmanian devil and the gray short-tailed opossum, we estimate that our transcriptome dataset represents approximately 15,000 koala genes. The marsupial alignment information was used to look for potential gene duplications and we report evidence for copy number expansion of the alpha amylase gene, and of an aldehyde reductase gene. Koala retrovirus (KoRV) transcripts were detected in the transcriptomes. These were analysed in detail and the structure of the spliced envelope gene transcript was determined. There was appreciable sequence diversity within KoRV, with 233 sites in the KoRV genome showing small insertions/deletions or single nucleotide polymorphisms. Both koalas had sequences from the KoRV-A subtype, but the male koala transcriptome has, in addition, sequences more closely related to the KoRV-B subtype. This is the first report of a KoRV-B-like sequence in a wild population. Conclusions This transcriptomic dataset is a useful resource for molecular genetic studies of the koala, for evolutionary genetic studies of marsupials, for validation and annotation of the koala genome sequence, and for investigation of koala retrovirus. Annotated transcripts can be browsed and queried at http://koalagenome.org

In the right space : exploring the dynamics between design, environment and pedagogy

The environments that we inhabit shape our everyday lives, influencing our behaviors and responses (Manu, 2013). As we enter an immersive phase of education in which physical and digital environments become inseparable, should we reconsider the role and importance of design on pedagogical practice? This paper explores the reciprocal cause and effect of space, technology and pedagogy in shaping the design of educational experiences within Queensland University of Technology's collaborative learning spaces.

Developing young students’ meta-representational competence through integrated mathematics and science investigations

This paper describes students’ developing meta-representational competence, drawn from the second phase of a longitudinal study, Transforming Children’s Mathematical and Scientific Development. A group of 21 highly able Grade 1 students was engaged in mathematics/science investigations as part of a data modelling program. A pedagogical approach focused on students’ interpretation of categorical and continuous data was implemented through researcher-directed weekly sessions over a 2-year period. Fine-grained analysis of the developmental features and explanations of their graphs showed that explicit pedagogical attention to conceptual differences between categorical and continuous data was critical to development of inferential reasoning.

Learning Chinese as a heritage language in Australia and beyond : the role of capital

The benefits of learning and retaining heritage languages are well documented in the literature. Chinese heritage language learners’ commitment to their heritage language learning has gained significant research ground in social psychological and post-structural schools, with empirical evidence predominantly emerging from the North American contexts. There is scant sociological examination of similar problems conducted outside North America. The current study aims to make a contribution in this regard. The use of Bourdieu's sociological notion of capital in the Australian context complements the social psychological and post-structural work predominantly produced in the North American contexts. The initial quantitative sub-study analyses the impacts of various resources on the Chinese heritage language proficiency of 230 snowball-sampled Chinese Australian respondents to an online survey. The subsequent qualitative sub-study explores the profits of learning Chinese heritage language through interviews with a subset of the survey sample. Findings indicate that cultural, social, and symbolic capital significantly positively contributes to Chinese Australians’ Chinese heritage language proficiency, which, in return, produces profits in different forms of capital. The study suggests a reciprocal relationship between ‘capital’ and Chinese heritage language proficiency.

Structuring representations of continuous data through investigations in grade 1

The study of data modelling with elementary students involves the analysis of a developmental process beginning with children’s investigations of meaningful contexts: visualising, structuring, and representing data and displaying data in simple graphs (English, 2012; Lehrer & Schauble, 2005; Makar, Bakker, & Ben-Zvi, 2011). A 3-year longitudinal study investigated young children’s data modelling, integrating mathematical and scientific investigations. One aspect of this study involved a researcher-led teaching experiment with 21 mathematically able Grade 1 students. The study aimed to describe explicit developmental features of students’ representations of continuous data...

Experimental Study of crack propagation in carbon steel using acoustic emission

Acoustic emission technique has become a significant and powerful structural health monitoring tool for structures. Researches to date have been done on crack location, fatigue crack propagation in materials and severity assessment of failure using acoustic emission technique. Determining severity of failure in steel structures using acoustic emission technique is still a challenge to accurately determine the relationship between the severity of crack propagation and acoustic emission activities. In this study three point bending test on low carbon steel samples along with acoustic emission technique have been used to determine crack propagation and severity. A notch is introduced at the tension face of the loading point to the samples to initiate the crack. The results show that the percentage of load drop of the steel specimen has a reciprocal relationship with the crack opening i.e. crack opening zones are influenced by the loading rate. In post yielding region, common acoustic emission signal parameters such as, signal strength, energy and amplitudes are found to be higher than those at pre-yielding and at yielding.