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.

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.

Evolutionary Perspectives

The standard approach to industrial economics starts with the industry’s basic conditions, then runs through the structure–conduct–performance paradigm of industrial organization, and finally considers government regulation and policy. Most creative industries segments have been studied in this way, for example in Albarran (2002) and Caves (2000). These approaches use standard economic analysis to explain the particular properties and characteristics of a specific industrial sector. The overview presented here is different again. It focuses on the creative industries and examines their economic effect, specifically their contribution to economic evolu -tion. This is an evolutionary systems approach to industrial analysis, where we seek to understand how a sector fits into a broader system of production, consumption, technology, trade and institutions. The evolutionary approach focuses on innovation, economic growth and endogenous transformation. So, rather than using economics to explain static or industrial-organization features of the creative industries, we are using an open systems view of the creative industries to explain dynamic ‘Schumpeterian’ features of the broader economy. The creative industries are drivers of economic transformation through their role in the origination of new ideas, in consumer adoption, and in facilitating the institutional embedding of new ideas into the economic order. This is not a novel idea, as economists have long understood that particular activities are drivers of economic growth and development, for example research and development, and also that particular sectors are instrumental to this process, for example high-technology sectors. What is new is the argument that cultural and creative sectors are also a key part of this process of economic evolution. We will review the case for that claim, and outline purported mechanisms. We will also consider why policy settings in the creative industries should be more in line with innovation and growth policy than with industry policy.

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.

Gas-phase reactions of aryl radicals with 2-butyne : an experimental and theoretical investigation employing the N-methyl-pyridinium-4-yl radical cation

Aromatic radicals form in a variety of reacting gas-phase systems, where their molecular weight growth reactions with unsaturated hydrocarbons are of considerable importance. We have investigated the ion-molecule reaction of the aromatic distonic N-methyl-pyridinium-4-yl (NMP) radical cation with 2-butyne (CH3C CCH3) using ion trap mass spectrometry. Comparison is made to high-level ab initio energy surfaces for the reaction of NMP and for the neutral phenyl radical system. The NMP radical cation reacts rapidly with 2-butyne at ambient temperature, due to the apparent absence of any barrier. The activated vinyl radical adduct predominantly dissociates via loss of a H atom, with lesser amounts of CH3 loss. High-resolution Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry allows us to identify small quantities of the collisionally deactivated reaction adduct. Statistical reaction rate theory calculations (master equation/RRKM theory) on the NMP + 2-butyne system support our experimental findings, and indicate a mechanism that predominantly involves an allylic resonance-stabilized radical formed via H atom shuttling between the aromatic ring and the C-4 side-chain, followed by cyclization and/or low-energy H atom beta-scission reactions. A similar mechanism is demonstrated for the neutral phenyl radical (Ph center dot)+2-butyne reaction, forming products that include 3-methylindene. The collisionally deactivated reaction adduct is predicted to be quenched in the form of a resonance-stabilized methylphenylallyl radical. Experiments using a 2,5-dichloro substituted methyl-pyridiniumyl radical cation revealed that in this case CH3 loss from the 2-butyne adduct is favoured over H atom loss, verifying the key role of ortho H atoms, and the shuttling mechanism, in the reactions of aromatic radicals with alkynes. As well as being useful phenyl radical analogues, pyridiniumyl radical cations may form in the ionosphere of Titan, where they could undergo rapid molecular weight growth reactions to yield polycyclic aromatic nitrogen hydrocarbons (PANHs).

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.

Permutation polynomials of the form (xp −x +δ)s +L(x)

Recently, several classes of permutation polynomials of the form (x2 + x + δ)s + x over F2m have been discovered. They are related to Kloosterman sums. In this paper, the permutation behavior of polynomials of the form (xp − x + δ)s + L(x) over Fpm is investigated, where L(x) is a linearized polynomial with coefficients in Fp. Six classes of permutation polynomials on F2m are derived. Three classes of permutation polynomials over F3m are also presented.

Exploring a biomimicry based approach and key barriers to evolving water infrastructure systems

Access to clean water is essential for human life and a critical issue facing much of modern society, especially as a result of the 21st Century triad of challenges – population growth, resource scarcity and pollution – which contribute to the rising complexity of providing adequate access to this essential resource for large parts of society. As such, there is now an increasing need for innovative solutions to source, treat and distribute water to cities across the globe. This position paper explores biomimicry – emulating natural form, function, process and systems – as an alternative and sustainable design approach to traditional water infrastructure systems. The key barriers to innovations such as biomimicry are summarised, indicating that regulatory and economic grounds are some of the major hindrances to integrating alternative design approaches in the water sector in developed countries. This paper examines some of the benefits of moving past these barriers to develop sustainable, efficient and resilient solutions that provide adequate access to water in the face of contemporary challenges.

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.

Smart material interfaces : a new form of physical interaction

Smart Material Interface (SMI) is the latest generation of user interface that makes use of engineered materials and leverages their special properties. SMIs are capable of changing their physical properties such as shape, size and color, and can be controlled under certain (external) conditions. We provide an example of such an SMI in the form of a prototype of a vacuum cleaner. The prototype uses schematic electrochromic polymer at the suction nozzle of the vacuum cleaner, which changes its color depending on the dust level on a floor. We emphasize on the new affordances and communication language supported by SMIs, which challenges the current metaphors of user interfaces in the field of HCI.

Electron capture of tetracyanoethylene oxide in the gas phase. Rearrangement of the parent radical anion to form [(NC)(3)C](-). A joint experimental and ab initio study

Capture of an electron by tetracyanoethylene oxide can initiate a number of decomposition pathways. One of these decompositions yields [(NC)3C]− as the ionic product. Ab initio calculations (at the B3LYP/6-31+G∗ level of theory) indicate that the formation of [(NC)3C]− is initiated by capture of an electron into the LUMO of tetracyanoethylene oxide to yield the anion radical [(NC)2C–O–C(CN)2]−· that undergoes internal nucleophilic substitution to form intermediate [(NC)3C–OCCN]−·. This intermediate dissociates to form [(NC)3C]− (m/z 90) as the ionic product. The radical (NC)3C· has an electron affinity of 4.0 eV (385 kJ mol−1). Ab initio calculations show that [(NC)3C]− is trigonal planar with the negative charge mainly on the nitrogens. A pictorial representation of this structure is the resonance structure formed from three degenerate contributing structures (NC)2–CCN−. The other product of the reaction is nominally (NCCO)·, but there is no definitive experimental evidence to indicate whether this radical survives intact, or decomposes to NC· and CO. The overall process [(NC)2C–O–C(CN)2]−· → [(NC)3C]− + (NCCO)· is calculated to be endothermic by 21 kJ mol−1 with an overall barrier of 268 kJ mol−1.

Assessment of gene expression of intracellular calcium channels, pumps and exchangers with epidermal growth factor-induced epithelial-mesenchymal transition in a breast cancer cell line

Background Epithelial-mesenchymal transition (EMT) is a process implicated in cancer metastasis that involves the conversion of epithelial cells to a more mesenchymal and invasive cell phenotype. In breast cancer cells EMT is associated with altered store-operated calcium influx and changes in calcium signalling mediated by activation of cell surface purinergic receptors. In this study, we investigated whether MDA-MB-468 breast cancer cells induced to undergo EMT exhibit changes in mRNA levels of calcium channels, pumps and exchangers located on intracellular calcium storing organelles, including the Golgi, mitochondria and endoplasmic reticulum (ER). Methods Epidermal growth factor (EGF) was used to induce EMT in MDA-MB-468 breast cancer cells. Serum-deprived cells were treated with EGF (50 ng/mL) for 12 h and gene expression was assessed using quantitative RT-PCR. Results and conclusions These data reveal no significant alterations in mRNA levels of the Golgi calcium pump secretory pathway calcium ATPases (SPCA1 and SPCA2), or the mitochondrial calcium uniporter (MCU) or Na+/Ca2+ exchanger (NCLX). However, EGF-induced EMT was associated with significant alterations in mRNA levels of specific ER calcium channels and pumps, including (sarco)-endoplasmic reticulum calcium ATPases (SERCAs), and inositol 1,4,5-trisphosphate receptor (IP3R) and ryanodine receptor (RYR) calcium channel isoforms. The most prominent change in gene expression between the epithelial and mesenchymal-like states was RYR2, which was enriched 45-fold in EGF-treated MDA-MB-468 cells. These findings indicate that EGF-induced EMT in breast cancer cells may be associated with major alterations in ER calcium homeostasis.