Sulfated glycosaminoglycans mediate the effects of FGF2 on the osteogenic potential of rat calvarial osteoprogenitor cells

Fibroblast growth factor-2 (FGF2) is a powerful promoter of bone growth. We demonstrate here that brief exposure to FGF2 enhances mineralized nodule formation in cultured rat osteoprogenitor cells due to an expansion of cells that subsequently mineralize. This mitogenic effect is mediated via sulfated glycosaminoglycans (GAGs), FGFR1, and the extracellular signal-regulated kinase (ERK) pathway. The GAGs involved in this stimulation are chondroitin sulfates (CS) rather than heparan sulfates (HS). However, continuous FGF2 treatment reduces alkaline phosphatase (ALP) activity, downregulates collagen Ialpha1 (ColIalpha1) and FGFR3 expression, upregulates the expression and secretion of osteopontin (OPN) and inhibits mineralization. The inhibitory effects of FGF2 on FGFR3 expression and ALP activity are also mediated by the ERK pathway, although the effects of FGF2 on ColIalpha1 and OPN expression are mediated by GAGs and PKC activity. Thus short-term activation of FGF2/FGFR1 promotes osteoprogenitor proliferation and subsequent differentiation, while long-term activation of FGF2 signaling disrupts mineralization by modulating osteogenic marker expression. This study thus establishes the central role of sulfated GAGs in the osteogenic progression of osteoprogenitors.

Exploring mediated interactions : a design exercise

With the emergence of personal and ubiquitous computing systems in the last decade, interaction designers have started designing products by employing quality oriented aspects such as user experience, playfulness, enchantment and others. In order to explore novel forms of mediated interactions, designers need to focus beyond the basic user requirements and usability issues. We present a procedure and results of a design exercise that we carried out with students of a master's course on Visual Design. Our intention was to explore new forms of mediated interaction by using a specific design exercise. We provide the details of the resulted design concepts and discuss the usefulness of our design exercise.

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.

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.

Physiological basis of salt stress tolerance in rice expressing the antiapoptotic gene SfIAP

Programmed cell death-associated genes, especially antiapoptosis-related genes have been reported to confer tolerance to a wide range of biotic and abiotic stresses in dicotyledonous plants such as tobacco (Nicotiana tabacum L.) and tomato (Solanum lycopersicum L.). This is the first time the antiapoptotic gene SfIAP was transformed into a monocotyledonous representative: rice (Oryza sativa L.). Transgenic rice strains expressing SfIAP were generated by the Agrobacterium-mediated transformation method and rice embryogenic calli, and assessed for their ability to confer tolerance to salt stress at both the seedling and reproductive stages using a combination of molecular, agronomical, physiological and biochemical techniques. The results show that plants expressing SfIAP have higher salt tolerance levels in comparison to the wild-type and vector controls. By preventing cell death at the onset of salt stress and maintaining the cell membrane’s integrity, SfIAP transgenic rice plants can retain plant water status, ion homeostasis, photosynthetic efficiency and growth to combat salinity successfully.

Halogen bond mediated crystal engineering of metal complexes

This project explored the potential for halogen bonds to predictably organise metal-containing molecular building blocks in crystalline materials. A novel method for the halogen bond mediated crystal engineering of metal complexes was discovered, which led to the preparation of new materials with potential applications in molecular switching devices and advanced memory storage systems.

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.

Homologs of FT, CEN and FD respond to developmental and environmental signals affecting growth and flowering in the perennial vine kiwifruit

FLOWERING LOCUS T (FT) and CENTRORADIALIS (CEN) homologs have been implicated in regulation of growth, determinacy and flowering. The roles of kiwifruit FT and CEN were explored using a combination of expression analysis, protein interactions, response to temperature in high-chill and low-chill kiwifruit cultivars and ectopic expression in Arabidopsis and Actinidia. The expression and activity of FT was opposite from that of CEN and incorporated an interaction with a FLOWERING LOCUS D (FD)-like bZIP transcription factor. Accumulation of FT transcript was associated with plant maturity and particular stages of leaf, flower and fruit development, but could be detected irrespective of the flowering process and failed to induce precocious flowering in transgenic kiwifruit. Instead, transgenic plants demonstrated reduced growth and survival rate. Accumulation of FT transcript was detected in dormant buds and stem in response to winter chilling. In contrast, FD in buds was reduced by exposure to cold. CEN transcript accumulated in developing latent buds, but declined before the onset of dormancy and delayed flowering when ectopically expressed in kiwifruit. Our results suggest roles for FT, CEN and FD in integration of developmental and environmental cues that affect dormancy, budbreak and flowering in kiwifruit.

Analysis of genetically modified red-fleshed apples reveals effects on growth and consumer attributes

Consumers of whole foods, such as fruits, demand consistent high quality and seek varieties with enhanced health properties, convenience or novel taste. We have raised the polyphenolic content of apple by genetic engineering of the anthocyanin pathway using the apple transcription factor MYB10. These apples have very high concentrations of foliar, flower and fruit anthocyanins, especially in the fruit peel. Independent lines were examined for impacts on tree growth, photosynthesis and fruit characteristics. Fruit were analysed for changes in metabolite and transcript levels. Fruit were also used in taste trials to study the consumer perception of such a novel apple. No negative taste attributes were associated with the elevated anthocyanins. Modification with this one gene provides near isogenic material and allows us to examine the effects on an established cultivar, with a view to enhancing consumer appeal independently of other fruit qualities. © 2012 Society for Experimental Biology, Association of Applied Biologists and Blackwell Publishing Ltd.

RNA interference silencing of CHS greatly alters the growth pattern of apple (Malus x domestica)

Plants produce a vast array of phenolic compounds which are essential for their survival on land. One major class of polyphenols are the flavonoids and their formation is dependent on the enzyme chalcone synthase (CHS). In a recent study we silenced the CHS genes of apple (Malus × domestica Borkh.) and observed a loss of pigmentation in the fruit skin, flowers and stems. More surprisingly, highly silenced lines were significantly reduced in size, with small leaves and shortened internode lengths. Chemical analysis also revealed that the transgenic shoots contained greatly reduced concentrations of flavonoids which are known to modulate auxin flow. An auxin transport study verified this, with an increased auxin transport in the CHS-silenced lines. Overall, these findings suggest that auxin transport in apple has adapted to take place in the presence of high endogenous concentrations of flavonoids. Removal of these compounds therefore results in abnormal auxin movement and a highly disrupted growth pattern. © 2013 Landes Bioscience.

pGreen : a versatile and flexible binary Ti vector for Agrobacterium-mediated plant transformation

Binary Ti vectors are the plasmid vectors of choice in Agrobacterium-mediated plant transformation protocols. The pGreen series of binary Ti vectors are configured for ease-of-use and to meet the demands of a wide range of transformation procedures for many plant species. This plasmid system allows any arrangement of selectable marker and reporter gene at the right and left T-DNA borders without compromising the choice of restriction sites for cloning, since the pGreen cloning sites are based on the well-known pBluescript general vector plasmids. Its size and copy number in Escherichia coli offers increased efficiencies in routine in vitro recombination procedures. pGreen can replicate in Agrobacterium only if another plasmid, pSoup, is co-resident in the same strain. pSoup provides replication functions in trans for pGreen. The removal of RepA and Mob functions has enabled the size of pGreen to be kept to a minimum. Versions of pGreen have been used to transform several plant species with the same efficiencies as other binary Ti vectors. Information on the pGreen plasmid system is supplemented by an Internet site (http://www.pgreen.ac.uk) through which comprehensive information, protocols, order forms and lists of different pGreen marker gene permutations can be found.