Osteogenic differentiation of murine embryonic stem cells is mediated by fibroblast growth factor receptors

The mechanisms involved in the control of embryonic stem (ES) cell differentiation are yet to be fully elucidated. However, it has become clear that the family of fibroblast growth factors (FGFs) are centrally involved. In this study we examined the role of the FGF receptors (FGFRs 1-4) during osteogenesis in murine ES cells. Single cells were obtained after the formation of embryoid bodies, cultured on gelatin-coated plates, and coaxed to differentiate along the osteogenic lineage. Upregulation of genes was analyzed at both the transcript and protein levels using gene array, relative-quantitative PCR (RQ-PCR), and Western blotting. Deposition of a mineralized matrix was evaluated with Alizarin Red staining. An FGFR1-specific antibody was generated and used to block FGFR1 activity in mES cells during osteogenic differentiation. Upon induction of osteogenic differentiation in mES cells, all four FGFRs were clearly upregulated at both the transcript and protein levels with a number of genes known to be involved in osteogenic differentiation including bone morphogenetic proteins (BMPs), collagen I, and Runx2. Cells were also capable of depositing a mineralized matrix, confirming the commitment of these cells to the osteogenic lineage. When FGFR1 activity was blocked, a reduction in cell proliferation and a coincident upregulation of Runx2 with enhanced mineralization of cultures was observed. These results indicate that FGFRs play critical roles in cell recruitment and differentiation during the process of osteogenesis in mES cells. In particular, the data indicate that FGFR1 plays a pivotal role in osteoblast lineage determination.

A question of agency : applying Sen’s theory of human capability to the concept of secondary school student career ‘choice’

In this paper, we seek to operationalize Amartya Sen's concept of human capability to guide a scholarly investigation of student career choice capability. We begin by outlining factors affecting youth labour markets in Australia; a prosperous country that is affected by a ‘two-speed’ national economy. We then examine recent government initiatives that have been designed to combat youth unemployment and cyclical disadvantage by enhancing the aspirations and career knowledge of secondary school students. We argue that these policy measures are based on four assumptions: first, that career choice capability is a problem of individual agency; second, that the dissemination of career information can empower students to act as ‘consumers’ in an unequal job market; third, that agency is simply a question of will; and finally, that school education and career advice – as a means to freedom in the space of career development – is of equal quality, distribution and value to an increasingly diverse range of upper secondary school students. The paper concludes by outlining a conceptual framework capable of informing an empirical research project that aims to test these assumptions by measuring and comparing differences between groups in the range of freedom to achieve and, therefore, to choose.

Integrin αvβ3 mediates upregulation of epidermal growth-factor receptor expression and activity in human ovarian cancer cells

Upon overexpression of integrin αvβ3 and its engagement by vitronectin, we previously showed enhanced adhesion, proliferation, and motility of human ovarian cancer cells. By studying differential expression of genes possibly related to these tumor biological events, we identified the epidermal growth-factor receptor (EGF-R) to be under control of αvβ3 expression levels. Thus in the present study we characterized αvβ3-dependent changes of EGF-R and found significant upregulation of its expression and activity which was reflected by prominent changes of EGF-R promoter activity. Upon disruption of DNA-binding motifs for the transcription factors p53, ETF, the repressor ETR, p50, and c-rel, respectively, we sought to identify DNA elements contributing to αvβ3-mediated EGF-R promoter induction. Both, the p53- and ETF-mutant, while exhibiting considerably lower EGF-R promoter activity than the wild type promoter, retained inducibility by αvβ3. Mutation of the repressor motif ETR, as expected, enhanced EGF-R promoter activity with a further moderate increase upon αvβ3 elevation. The p50-mutant displayed EGF-R promoter activity almost comparable to that of the wild type promoter with no impairment of induction by αvβ3. However, the activity of an EGF-R promoter mutant displaying a disrupted c-rel-binding motif did not only prominently decline, but, moreover, was not longer responsive to enhanced αvβ3, involving this DNA element in αvβ3-dependent EGF-R upregulation. Moreover, αvβ3 did not only increase the EGF-R but, moreover, also led to obvious co-clustering on the cancer cell surface. By studying αvβ3/EGF-R-effects on the focal adhesion kinase (FAK) and the mitogen activated protein kinases (MAPK) p44/42 (erk−1/erk−2), having important functions in synergistic crosstalk between integrins and growth-factor receptors, we found for both significant enhancement of expression and activity upon αvβ3/VN interaction and cell stimulation by EGF. Upregulation of the EGF-R by integrin αvβ3, both receptor molecules with a well-defined role as targets for cancer treatment, might represent an additional mechanism to adapt synergistic receptor signaling and crosstalk in response to an altered tumor cell microenvironment during ovarian cancer progression.

School nurses and partnerships for health education : team teaching in the secondary school curricula

The purpose of this research is to examine School Based Youth Health Nurses experience of partnerships for health education and team teaching. The School Based Youth Health Nurse Program is a contemporary model of school nursing in Queensland, Australia. The role of the School Based Youth Health Nurse consists of individual health consultations and health promotion. This research analyses a subset of qualitative data collected for a larger project about the experience of school based youth health nursing. The Health Promoting Schools model is used as a deductive framework. The findings reveal five subthemes across the three areas of the Health Promoting Schools approach. There are two subthemes within the curriculum, teaching and learning area; We were on the same page so to speak and I can go and do my reports or whatever. There are two sub-themes within the partnerships and services area; I had a beautiful science teacher who was just delightful and really just wanted to do things in partnerships and It’s all airy fairy arty farty stuff that’s not important. There is one theme in the school organisation, ethos and environment area; I just don’t know how well the top of these organisations communicate with the bottom of those organisations. Successful partnerships for health education and team teaching between school nurses and teachers are based on personal relationships based on rapport which lead to trust and reciprocity. Partnerships are limited by teachers understanding of the role of the school nurse and engagement with school nurses in the classroom. Administrative support from the top down is fundamental.

Promoting resilience and posttraumatic growth in medical professionals

Across the lifespan traumatic experiences are common with more people experiencing such events than not. Within the context of being a medical professional trauma may result from a direct experience (e.g., in a person’s personal life) but may also occur vicariously. For example, a medical professional may be traumatized during the course of their employ as they come to the aid of a trauma survivor. Although there can be long term negative sequale for trauma survivors (e.g., PTSD, depression), the majority of people who experience trauma, vicariously or otherwise, are resilient to long term effects and some people grow or develop beyond their pre-event level of functioning. Therefore, in addition to interest in antecedents and correlates of pathology, research examining the predictors and correlates of resilience and growth has gained notable attention. In this chapter the fundamental assumptions of the salutogenic theory are discussed. Salutogenisis refers to the study of the origins of health and to that end has a goal to determine factors involved in promoting and maintaining health. The chapter then goes on to describe posttraumatic growth, a term used to denote positive post-trauma changes as well as resilience including discussion of the similarities and differences between these two constructs. Ways of promoting growth and resilience in medical professionals are then identified. The chapter concludes with discussion of ways in which individuals can enhance their potential for growth and also of ways in which the organization they work for can best facilitate and promote resilience and growth in its employees.

Mechanical tension as a driver of connective tissue growth in vitro

We propose the progressive mechanical expansion of cell-derived tissue analogues as a novel, growth-based approach to in vitro tissue engineering. The prevailing approach to producing tissue in vitro is to culture cells in an exogenous “scaffold” that provides a basic structure and mechanical support. This necessarily pre-defines the final size of the implantable material, and specific signals must be provided to stimulate appropriate cell growth, differentiation and matrix formation. In contrast, surgical skin expansion, driven by increments of stretch, produces increasing quantities of tissue without trauma or inflammation. This suggests that connective tissue cells have the innate ability to produce growth in response to elevated tension. We posit that this capacity is maintained in vitro, and that order-of-magnitude growth may be similarly attained in self-assembling cultures of cells and their own extracellular matrix. The hypothesis that growth of connective tissue analogues can be induced by mechanical expansion in vitro may be divided into three components: (1) tension stimulates cell proliferation and extracellular matrix synthesis; (2) the corresponding volume increase will relax the tension imparted by a fixed displacement; (3) the repeated application of static stretch will produce sustained growth and a tissue structure adapted to the tensile loading. Connective tissues exist in a state of residual tension, which is actively maintained by resident cells such as fibroblasts. Studies in vitro and in vivo have demonstrated that cellular survival, reproduction, and matrix synthesis and degradation are regulated by the mechanical environment. Order-of-magnitude increases in both bone and skin volume have been achieved clinically through staged expansion protocols, demonstrating that tension-driven growth can be sustained over prolonged periods. Furthermore, cell-derived tissue analogues have demonstrated mechanically advantageous structural adaptation in response to applied loading. Together, these data suggest that a program of incremental stretch constitutes an appealing way to replicate tissue growth in cell culture, by harnessing the constituent cells’ innate mechanical responsiveness. In addition to offering a platform to study the growth and structural adaptation of connective tissues, tension-driven growth presents a novel approach to in vitro tissue engineering. Because the supporting structure is secreted and organised by the cells themselves, growth is not restricted by a “scaffold” of fixed size. This also minimises potential adverse reactions to exogenous materials upon implantation. Most importantly, we posit that the growth induced by progressive stretch will allow substantial volumes of connective tissue to be produced from relatively small initial cell numbers.

Quantitative genetic parameters for body traits at different ages in a cultured stock of giant freshwater prawn (Macrobrachium rosenbergii) selected for fast growth

The aim of the current study was to estimate heritabilities and correlations for body traits at different ages (Weeks 10 and 18 after stocking) in a giant freshwater prawn (Macrobrachium rosenbergii) population selected for fast growth rate in Vietnam. The dataset consisted of 4650 body records (2432 and 2218 records collected at Weeks 10 and 18, respectively) in the full pedigree comprising a total of 18 387 records. Variance and covariance components were estimated using restricted maximum likelihood fitting a multi-trait animal model. Estimates of heritability for body traits (bodyweight, body length, cephalothorax length, abdominal length, cephalothorax width and abdominal width) were moderate and ranged from 0.06 to 0.11 and from 0.11 to 0.22 at Weeks 10 and 18, respectively. Body-trait heritabilities estimated at Week 10 were not significantly lower than at Week 18. Genetic correlations between body traits within age and genetic correlations for body traits between ages were generally high. Our results suggested that selection for high growth rate in GFP can be undertaken successfully before full market size has been reached.

Distress, coping and posttraumatic growth in refugees from Burma

Refugees flee their countries of origin due to supreme hardship and threat to life; frequently bearing witness to mass atrocity. This research is embedded in a salutogenic paradigm which emphasises strength and adjustment. Twenty-five refugees from Burma who were newly arrived in Australia were interviewed and transcripts were analysed using an Interpretive Phenomenological Analytic (IPA) approach. In addition to themes of distress, data revealed an extraordinary adaptive capacity and highlighted strengths, both individually and collectively. Specific adaptive strategies included religiousness, and a sense of duty to family, community and country. Findings have implications for policy and practice that aim to support refugees and asylum seekers.

Cents and Sustainability : Securing Our Common Future by Decoupling Economic Growth from Environmental Pressures

The focus of Cents and Sustainability is to respond to the call by Dr Gro Brundtland in the seminal book Our Common Future to achieve, 'a new era of economic growth - growth that is forceful and at the same time socially and environmentally sustainable'. With the 20th anniversary of Our Common Future in 2007, it is clearly time to re-examine this important work in a modern global context. Using the framework of ‘Decoupling Economic Growth from Environmental Pressures’, Cents and Sustainability investigates a range of new evidence and research in order to develop a deeper understanding of how, and under what conditions, this 'forceful sustainable growth' is possible. With an introduction by Dr Jim MacNeill (former Secretary General to the Brundtland Commission, and former Director, OECD Environment Directorate 1978 -1984), the book will carry forewords from Dr Gro Brundtland (former Chair of the World Commission on Environment and Development), Dr Rajendra Pachauri (Chief, Intergovernmental Panel on Climate Change (IPCC), and joint recipient of the 2007 Nobel Peace Prize on behalf of the IPCC), and Dr Kenneth Ruffing (former Deputy Director and Chief Economist of the OECD Environment Directorate 2000 - 2005). Beginning with a detailed explanation of decoupling theory, along with investigation into a range of issues and barriers to its achievement, the book then focuses on informing national strategies for decoupling. Then putting this into action the book focuses on five key areas of decoupling, namely greenhouse gas emissions, biodiversity, freshwater extraction, waste production, and air pollution, and in each case showing compelling evidence for significant cost effective reductions in environmental pressures. The book concludes with a detailed case study of the groundbreaking application of public interest litigation to combat air pollution in Delhi, India.

Database relation watermarking resilient against secondary watermarking attacks

There has been tremendous interest in watermarking multimedia content during the past two decades, mainly for proving ownership and detecting tamper. Digital fingerprinting, that deals with identifying malicious user(s), has also received significant attention. While extensive work has been carried out in watermarking of images, other multimedia objects still have enormous research potential. Watermarking database relations is one of the several areas which demand research focus owing to the commercial implications of database theft. Recently, there has been little progress in database watermarking, with most of the watermarking schemes modeled after the irreversible database watermarking scheme proposed by Agrawal and Kiernan. Reversibility is the ability to re-generate the original (unmarked) relation from the watermarked relation using a secret key. As explained in our paper, reversible watermarking schemes provide greater security against secondary watermarking attacks, where an attacker watermarks an already marked relation in an attempt to erase the original watermark. This paper proposes an improvement over the reversible and blind watermarking scheme presented in [5], identifying and eliminating a critical problem with the previous model. Experiments showing that the average watermark detection rate is around 91% even with attacker distorting half of the attributes. The current scheme provides security against secondary watermarking attacks.

Productivity differences, technology adoption and economic growth : the case of India

When the acronym of ëBRICí was coined in 2001 by Jim OíNeill of Goldman Sachs, it was expected that economic growth rates in India, Brazil and Russia would eventually catch up with that of China. However, China has continued to outperform the other economies in the group, even after it was renamed ëBRICSí to reflect the inclusion of South Africa in 2010. The focus of this chapter is on one of the BRICS economies, namely India. Its aim is to examine from an economic perspective, why Indiaís performance has not lived up to expectations, and comment on the key challenges it faces in meeting them. We begin with some descriptive statistics regarding the progress of the Indian economy since 1990. While it has been growing at a rapid rate since the reforms it introduced in the1990s, there has been a slowdown in its overall GDP growth rates since 2008. The rate of growth experienced in the period 2003ñ07 was an average of 10.5 per cent. However, since the recession following the Global Financial Crisis (GFC) of 2008, the growth rate has fallen. From the period 2008ñ12 it has only registered an average growth rate of 6.5 per cent (World Bank, 2013). This chapter suggests that one of the major factors underpinning this slowdown is the performance of Indiaís agricultural sector. The importance of the agricultural sector is highlighted by the following stylized facts.

Antibodies mediate formation of neutrophil extracellular traps in the middle ear and facilitate secondary pneumococcal otitis media

Otitis media (OM) (a middle ear infection) is a common childhood illness that can leave some children with permanent hearing loss. OM can arise following infection with a variety of different pathogens, including a coinfection with influenza A virus (IAV) and Streptococcus pneumoniae (the pneumococcus). We and others have demonstrated that coinfection with IAV facilitates the replication of pneumococci in the middle ear. Specifically, we used a mouse model of OM to show that IAV facilitates the outgrowth of S. pneumoniae in the middle ear by inducing middle ear inflammation. Here, we seek to understand how the host inflammatory response facilitates bacterial outgrowth in the middle ear. Using B cell-deficient infant mice, we show that antibodies play a crucial role in facilitating pneumococcal replication. We subsequently show that this is due to antibody-dependent neutrophil extracellular trap (NET) formation in the middle ear, which, instead of clearing the infection, allows the bacteria to replicate. We further demonstrate the importance of these NETs as a potential therapeutic target through the transtympanic administration of a DNase, which effectively reduces the bacterial load in the middle ear. Taken together, these data provide novel insight into how pneumococci are able to replicate in the middle ear cavity and induce disease.

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.