Fibroblast growth factor 2 restrains ras-driven proliferation of malignant cells by triggering RhoA-mediated senescence

Fibroblast growth factor 2 (FGF2) is considered to be a bona fide oncogenic factor, although results from our group and others call this into question. Here, we report that exogenous recombinant FGF2 irreversibly inhibits proliferation by inducing senescence in Ras-dependent malignant mouse cells, but not in immortalized nontumorigenic cell lines. We report the following findings in K-Ras-dependent malignant YI adrenocortical cells and H-Ras V12-transformed BALB-3T3 fibroblasts: (a) FGF2 inhibits clonal growth and tumor onset in nude and immunocompetent BALB/c mice, (b) FGF2 irreversibly blocks the cell cycle, and (c) FGF2 induces the senescence-associated -galactosidase with no accompanying signs of apoptosis or necrosis. The tyrosine kinase inhibitor PD173074 completely protected malignant cells from FGF2. In Yl adrenal cells, reducing the constitutively high levels of K-Ras-GTP using the dominant-negative RasN17 mutant made cells resistant to FGF2 cytotoxicity. In addition, transfection of the dominant-negative RhoA-N19 into either YI or 3T3-B61 malignant cell lines yielded stable clonal transfectants that were unable to activate RhoA and were resistant to the FGF2 stress response. We conclude that in Rasdependent malignant cells, FGF2 interacts with its cognate receptors to trigger a senescence-like process involving RboAGTP. Surprisingly, attempts to select FGF2-resistant cells from the Yl and 3T3-B61 cell lines yielded only rare clones that (a) had lost the overexpressed ras oncogene, (b) were dependent on FGF2 for proliferation, and (c) were poorly tumorigenic. Thus, FGF2 exerted a strong negative selection that Rasdependent malignant cells could rarely overcome.

Serum amyloid A induces reactive oxygen species (ROS) production and proliferation of fibroblast

Serum amyloid A (SAA) levels are elevated highly in acute phase response and elevated slightly and persistently in chronic diseases such as rheumatoid arthritis and diabetes. Given that fibroblasts exert profound effects on progression of inflammatory chronic diseases, the aim of this study was to investigate the response of fibroblasts to SAA. A dose-dependent increase in O(2)(-) levels was observed by treatment of fibroblasts with SAA (r = 0.99 and P <= 0.001). In addition, the expression of p47-phox was up-regulated by SAA (P < 0.001) and diphenyliodonium (DPI), a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, reduced the release of O(2)(-) by 50%. Also, SAA raised fibroblast proliferation (P < 0.001) and this effect was completely abolished by the addition of anti-oxidants (P < 0.001). These findings support the notion that, in chronic inflammatory sites, SAA activated fibroblast proliferation and ROS production.

Effect of cold storage on culture viability and some rheological properties of fermented milk prepared with yogurt and probiotic bacteria

We examined the effect of storage time on culture viability and some rheological properties (yield stress, storage modulus, loss modulus, linear viscoelastic region, structural recuperation and firmness) of fermented milk made with Lactobacillus delbrueckii ssp. bulgaricus, Lactobacillus acidophilus (LA) and Bifidobacterium animalis ssp. lactis in coculture with Streptococcus thermophilus (ST). Acidification profiles and factors that affect viability (postfermentation acidification, acidity and dissolved oxygen) were also studied during 35 days at 4C. Fermented milk prepared with a coculture of ST and Bifidobacterium lactis gave the most constant rheological behavior and the best cell viability during cold storage; it was superior to ST plus LA for probiotic fermented milk production.

Effects of alloying elements on the cytotoxic response of titanium alloys

Titanium alloys, alloys, especially beta-type alloys containing beta-stabilizing elements, constitute a highly versatile category of metallic materials that have been under constant development for application in orthopedics and dentistry. This type of alloy generally presents a high mechanical strength-to-weight ratio, excellent corrosion resistance and low elastic modulus. The purpose of this study is to evaluate the cytotoxicity and adhesion of fibroblast cells on titanium alloy substrates containing Nb, Ta, Zr, Cu, Sn and Mo alloying elements. Cells cultured on polystyrene were used as controls. In vitro results with Vero cells demonstrated that the tested materials, except Cu-based alloy, presented high viability in short-term testing. Adhesion of cells cultured on disks showed no differences between the materials and reference except for the Ti-Cu alloy, which showed reduced adhesion attributed to poor metabolic activity. Titanium alloys with the addition of Nb, Ta, Zr, Sn and Mo elements show a promising potential for biomedical applications. (C) 2011 Elsevier B.V. All rights reserved.

Relationship marketing, audience retention and performing arts organisation viability

Marketing strategy in performing arts organisations has become particularly important in the increasingly competitive environment in which the arts operate. Since the late 1980s there has been a necessary shift in focus to audience development away from product development. This change in focus is being encouraged to ensure the long-term viability of performing arts organisations (PAOs) and micro-economic reform. While government reports have recommended strategies aimed at building audience based recognition, this is an expensive approach for many PAOs and does not produce short term returns. Little attention has been paid to building enduring relationships with existing audiences as a way if having a more dramatic impact on PAOs' long-term viability. This paper explores this theme through relationship marketing and the implication of retaining existing audiences. The paper identifies the changing cultural environment which has led to the importance if marketing. It then explains the concepts if relationship marketing and its pertinence to PAOs' viability by presenting a loyalty ladder. The structure is modelled as a dynamic conceptualisation of the relationships (audience and organisation) to assist arts managers to decide whether to focus their efforts on catching or keeping customers to maximise earned income.

Pricing in the museum sector : the need to balance social responsibility and organisational viability

An essential component of marketing strategy is pricing. Pricing in museums, however, is problematic as issues beyond cost recovery or surplus, such as social responsibilities, need to be considered. This area of marketing is under researched. The aim of this study is to address the research gap by synthesising the literature on pricing strategy in the museum sector. The study found that there are a number of strategies being advocated with regard to pricing in the museum sector in the literature, each representing various perspectives of museology. A research agenda was proposed to assist marketers in the museum sector to meet their organisational needs, whilst balancing their social responsibilities.

Analysis of Optimum Location, Viability, and Potential Effects of Wind Farm Construction in Maine

Maine has the highest potential for wind energy in New England and falls within the top twenty states in the nation. It falls just behind Wisconsin and California with an estimate electrical output of 56 billion kWhs. The geological makeup of Maine’s mountains in the western part of the state, and the exposed coastline provide opportune areas to capture wind and convert it into energy. The information included in this poster will suggest the most likely areas for wind development based on a number of factors as recommended by the American Wind Energy Association.

EBanking adaptation and dot.com viability : a comparison of Australian and Indian experiences in the banking sector

With the advent of widely-accepted eBusiness activities, many banks have floated dot.com entities to create a presence on the Internet and take advantage of its power and reach. Like many other businesses, banks expected an increase in market capitalisation as a result of their dot.com floats, perceived broadly as a measure of growing profitability. Despite the negative publicity that the recent spate of dot.com crashes has generated, banks seem to continue floating online spin-offs. Our exploratory study investigates this phenomenon, studying the drivers for change in the evolution of the banking sector, and the move towards electronic banking. We focussed on two economies – Australia and India – to aggregate the major factors in this evolution from the perspective of two disparate economies.

The paper describes our qualitative, document-based investigation of the Australian and Indian banking sectors, and subsequent quantitative analysis of the impact of dot.com floats on market capitalisation within this market sector. We then describe the effect of applying both Transaction Cost Economics to our findings, which indicates that the cost of transacting business has been reduced overall by the creation of dot.com entities; and “catch-up, fall-behind, forge ahead” theory to gain an economic perspective. The paper provides both practical assistance for banks in making decisions regarding e-portfolios, as well as for policy makers in the economies reviewed; and has the potential to contribute to academic research into eBanking more generally.

Dispersal of Hormosira banksii (phaeophyceae) via detached fragments : reproductive viability and longevity

Drifting, fertile thalli are well documented to be the primary long-distance dispersal vector for many marine macroalgae, but little information about reproductive viability of drift is known. This study examined the reproductive viability and longevity of floating fragments of the intertidal Australasian fucoid Hormosira banksii (Turner) Decne. Beach wrack surveys and field experiments were conducted to test the model that long-distance dispersal is achieved in H. banksii via floating, fertile fronds. High densities of beach wrack fragments were evident during summer compared to autumn. The majority of beach wrack occurred on sandy beaches rather than rocky shores. Both male and female fragments were present in the beach wrack. Detached fronds were capable of releasing gametes up to 8 weeks after detachment. Beach wrack produced high fertilization rates and recruited successfully onto artificial panels. Results suggest that detached fragments are reproductively viable and that floating, fertile fronds may be an important mechanism for facilitating long-distance dispersal in this species. Nevertheless, the frequency of fronds reaching a suitable habitat and contributing to gene flow between populations, or colonizing new populations, may not be proportional to the total density of beach wrack.

An evaluation of the viability of photovoltaics in residential schemes managed by UK registered social landlords

Global demands on fossil fuels require the investigation of renewable and viable alternative energy supplies. The Intergovernmental Panel on Climate Change (IPCC) has concluded that current consumption of fossil fuels is untenable as atmospheric emissions of gases, in particular carbon dioxide (CO²), is having a significant and worsening effect on global climate change (IPCC 1992).

25% of UK CO² emissions are generated in the housing sector (UKCCP 2000). As major providers of UK social housing, Registered Social Landlords (RSLs), indirectly make a significant contribution to UK CO² emissions. In delivering UK Government policies, RSLs are required to meet national social and economic targets, as well as environmental targets. Clearly, social, environmental and economic issues combine in the arena of energy efficiency and social housing.

Potentially, the use of photovoltaics (PV) in social housing could assist the UK government in meeting targets in terms of affordable housing, providing "free" electricity to low income tenants, and with minimal environmental impact in urban areas. However, uptake of PV amongst RSLs in the UK has been minimal to date. This paper explores the factors that act as barriers to energy efficiency in this market.

Fibroblast growth factor-2 over-rides insulin-like growth factor-I induced proliferation and cell survival in human neuroblastoma cells

The insulin-like growth factor (IGF) system is a key regulator of cell growth, survival and differentiation, and these functions are co-modulated by other growth factors including fibroblast growth factor-2 (FGF-2). To investigate IGF/FGF interactions in neuronal cells, we employed neuroblastoma cells (SK-N-MC). In serum free conditions proliferation of the SK-N-MC cells was promoted by IGF-I (25 ng/ml), but blunted by FGF-2 (50 ng/ml). IGF-I-induced proliferation was abolished in the presence of FGF-2 even when IGF-I was used at 100 ng/ml. In addition to our previously described FGF-2 induced proteolytic cleavage of IGFBP-2, we found that FGF-2 increased IGFBP-6 levels in conditioned medium (CM) without affecting IGFBP-6 mRNA abundance. Modulation of IGFBP-2 and -6 levels were not significant mechanisms involved in the blockade of IGF-I action since the potent IGF-I analogues [QAYL]IGF-I and des(1-3)IGF-I (minimal IGFBP affinity) were unable to overcome FGF-2 inhibition of cell proliferation. FGF-2 treated cells showed morphological differentiation expressing the TUJ1 neuronal marker while cells treated with IGF-I alone showed no morphological change. When IGF-I was combined with FGF-2, however, cell morphology was indistinguishable from that seen with FGF-2 alone. FGF-2 inhibited proliferation and enhanced differentiation was also associated with a 70% increase in cell death. Although IGF-I alone was potently anti-apoptotic (60% decreased), IGF-I was unable to prevent apoptosis when administrated in combination with FGF-2. Gene-array analysis confirmed FGF-2 activation of the intrinsic and extrinsic apoptotic pathways and blockade of IGF anti-apoptotic signaling. FGF-2, directly and indirectly, overcomes the proliferative and anti-apoptotic activity of IGF-I by complex mechanisms, including enhancement of differentiation and apoptotic pathways, and inhibition of IGF-I induced anti-apoptotic signalling. Modulation of IGF binding protein abundance by FGF-2 does not play a significant role in inhibition of IGF-I induced mitogenesis.

Sperm competition and offspring viability at hybridization in Australian tree frogs, Litoria peronii and L. tyleri

Hybridization between closely related species often leads to reduced viability or fertility of offspring. Complete failure of hybrid offspring (post-zygotic hybrid incompatibilities) may have an important role in maintaining the integrity of reproductive barriers between closely related species. We show elsewhere that in Peron's tree frog, Litoria peronii, males more closely related to a female sire more offspring in sperm competition with a less related rival male. Observations of rare 'phenotypic intermediate' males between L. peronii and the closely related L. tyleri made us suggest that these relatedness effects on siring success may be because of selection arising from risks of costly hybridization between the two species. Here, we test this hypothesis in an extensive sperm competition experiment, which shows that there is no effect of species identity on probability of fertilization in sperm competition trials controlling for sperm concentration and sperm viability. Instead, there was a close agreement between a male's siring success in isolation with a female and his siring success with the same female in competition with a rival male regardless of species identity. Offspring viability and survival, however, were strongly influenced by species identity. Over a 14-day period, hybrid offspring suffered increasing mortality and developed more malformations and an obvious inability to swim and right themselves, leading to compromised probability of survival. Thus, hybridization in these sympatric tree frogs does not compromise fertilization but has a strong impact on offspring viability and opportunity for reinforcement selection on mate choice for conspecific partners.

Male and female effects on fertilization success and offspring viability in the Peron's tree frog, Litoria peronii

There is increasing theoretical and empirical evidence that genetic compatibility among partners is an important determinant of fertilization success and offspring viability. In amphibians, females often actively choose partners from among a variety of males and polyandry is common. Genetic compatibility among partners may therefore be an important determinant of fertilization success and offspring viability in some amphibians. Amphibians also show some of the highest levels of genetic differentiation among neighbouring populations known in vertebrates, and as such, populations may have evolved different co-adapted gene complexes. This means that offspring from among-population crosses may have reduced fitness. It is therefore essential to understand to what extent crossings between and within populations may interfere with successful fertilization and offspring viability. Here, we test whether crossing individuals within and between two different populations of the Australian Peron's tree frog (Litoria peronii) using artificial fertilizations affect fertilization success and offspring viability. Fertilization success per se is strongly influenced by male identity, which is likely to depend at least to some extent on the experimental procedure (e.g. resulting in variation in sperm number per ejaculate), whereas there was no fertilization effect of female identity. More importantly, male and female identity, independently of each other, explained significant variation in offspring viability, whereas no such effect could be linked to population of origin. Thus, our experiments suggest that crossing populations may not always be the most significant factor affecting fertilization success or offspring viability, but may be more influenced by the genetic quality or the genetic compatibility of partners.

The viability of commercial tomato production in the Autopot system

An investigation of the viability of commercial tomato production using the Autopot growing system in Australia. The Autopot system is a relatively new hydroponic production system technology that is being introduced onto the market in competition with traditional systems. Although commercial tomato production was found to be significantly more water and nutrient efficient in the Autopot system than in a traditional open system, yields were significantly lower. Financial modelling shows that tomato production in this system would not be commercially viable in Australia for a typical tomato growing venture under current conditions.