Osteopontin is required for full expression of the transformed phenotype by the ras oncogene

The secreted phosphoprotein osteopontin (OPN) is strongly associated with the process of neoplastic transformation, based both on its pattern of expression in vivo and in vitro and on functional analyses. We have used 3T3 cells derived from wildtype and OPN-deficient mice and transformed by transfection with oncogenic ras to assess the role of OPN in transformation in vitro and in tumorigenesis in vivo. There was no effect of an absence of OPN on the ability of the cells to undergo immortalization or to form morphologically transformed foci following ras transfection. Wildtype and OPN-deficient cell lines were established from such foci, and lines with similar ras mRNA levels selected for further analysis. Ras -transformed cell lines from both wildtype and OPN-deficient mice could form colonies in soft agar indicating that this process can occur in the absence of OPN. However, the ability of the OPN-deficient cell lines to form colonies was reduced as compared to wildtype cell lines. Tumorigenesis in syngeneic and nude mice was assessed for a subset of cell lines that formed colonies efficiently in soft agar. Cell lines unable to make OPN formed tumors in these mice much more slowly than wildtype cells, despite similar growth of the cells on plastic and in soft agar. Taken together, these results indicate that maximal transformation by ras requires OPN expression, and implicate increased OPN expression as an important effector of the transforming activity of the ras oncogene. © 2000 Cancer Research Campaig

Developing Absorptive Capacity Theory for Public Service Organizations:Emerging UK Empirical Evidence

A strong public policy focus on high performance means that utilizing management knowledge effectively is at a premium for UK public service organizations. This study empirically examined two English public agencies to explore the inter-sectoral transfer of a strategic management model originally developed in the private sector – absorptive capacity – which is one way of conceptualizing an organizational competence in such knowledge mobilization. Two theoretical contributions are made. First, a new absorptive capacity framework for public service organizations is developed which recognizes the participation of public agency project teams during an innovation process proceeding over time with phases of co-creation, testing, metamorphosis and diffusion. Second, our novel framework modifies an early influential model of absorptive capacity. Counter to this model, we argue that realized absorptive capacity requires agency from skilled and embedded actors to turn ‘curbing routines’ into ‘enabling routines’ in all four stages. Project (middle) managers have flexibility in their roles to seize episodic moments of opportunity to innovate and achieve service delivery goals, and to build absorptive capacity capability. Absorptive capacity capability develops organically over time. Future research directions are discussed

Chromosome assignment of two cloned DNA probes hybridizing predominantly to human sex chromosomes

In situ hybridization experiments were carried out with two clones, YACG 35 and 2.8, which had been selected from two genomic libraries strongly enriched for the human Y chromosome. Besides the human Y chromosome, both sequences strongly hybridized to the human X chromosome, with few minor binding sites on autosomes. In particular, on the X chromosome DNA from clone YACG 35 hybridized to the centromeric region and the distal part of the short arm (Xp2.2). On the Y chromosome, the sequence was assigned to one site situated in the border region between Yq1.1 and Yq1.2. DNA from clone 2.8 also hybridized to the centromeric region of the X and the distal part of the short arm (Xq2.2). On the Y, however, two binding sites were observed (Yp1.1 and Yq1.2). The findings indicate that sex chromosomal sequences may be localized in homologous regions (as suggested from meiotic pairing) but also at ectopic sites

Recombinant human osteopontin expressed in Nicotiana benthamiana stimulates osteogenesis related genes in human periodontal ligament cells.

Tissue engineering aims to utilise biologic mediators to facilitate tissue regeneration. Several recombinant proteins have potential to mediate induction of bone production, however, the high production cost of mammalian cell expression impedes patient access to such treatments. The aim of this study is to produce recombinant human osteopontin (hOPN) in plants for inducing dental bone regeneration. The expression host was Nicotiana benthamiana using a geminiviral vector for transient expression. OPN expression was confirmed by Western blot and ELISA, and OPN was purified using Ni affinity chromatography. Structural analysis indicated that plant-produced hOPN had a structure similar to commercial HEK cell-produced hOPN. Biological function of the plant-produced hOPN was also examined. Human periodontal ligament stem cells were seeded on an OPN-coated surface. The results indicated that cells could grow normally on plant-produced hOPN as compared to commercial HEK cell-produced hOPN determined by MTT assay. Interestingly, increased expression of osteogenic differentiation-related genes, including OSX, DMP1, and Wnt3a, was observed by realtime PCR. These results show the potential of plant-produced OPN to induce osteogenic differentiation of stem cells from periodontal ligament in vitro, and suggest a therapeutic strategy for bone regeneration in the future

Punctuated equilibrium theory in Brazilian public policy: the case of Ceará

Este artigo faz uma análise do processo de decisão orçamental dos municípios do Estado do Ceará. Através deste estudo, procura-se perceber em que medida a distribuição dos orçamentos aos governos locais sofrem (ou não) variações. Já em um segundo momento, tenta-se depreender quais as receitas de cada um dos municípios (as variáveis independentes) que melhor descrevem e auxiliam a opção política de investimento local (esta será a variável dependente). Considerando o período de 2006 a 2010 e fazendo uso de um desenho de pesquisa de tipo transversal, conclui-se que nos governos locais do Ceará o investimento público apresenta períodos de estabilidade seguido por períodos de grande alteração dos orçamentos – confirmando a hipótese de pesquisa. Estas conclusões confirmam os pressupostos da teoria do equilíbrio pontuado. Conclui-se igualmente que o investimento público que vem sendo realizado é dependente das transferências que a União faz para os governos locais do Estado do Ceará e das receitas de capital. Face a estas condições, é pertinente equacionar até que nível e grau o endividamento pode ocorrer em virtude da escassez cada vez maior do financiamento público.This research aims to analyze the budget decision process in Ceará municipalities in order to understand in which way budget distributions change (or not) during the research period under consideration. This research also aims to understand which revenues (the independent variables) of each municipality better expla in the political choices for local government investments (the dependent variable). Making use of data from 2006 to 2010 and using a cross - sectional research design, the study concludes a stability in local government investments periods of stress where su ch investments have both positive and negative significant fluctuations – confirming our working hypothesis. These results confirm punctuated Equilibrium Theory assumptions and also find that local government public investment is dependent on money transfe rs from the central government and also from capital revenues. Thus, it is important to question to what degree public indebtedness should be allowed, due to a scarcity of public fundsinfo:eu-repo/semantics/publishedVersio

Motivation and incentives of rural maternal and neonatal health care providers: a comparison of qualitative findings from Burkina Faso, Ghana and Tanzania.

In Burkina Faso, Ghana and Tanzania strong efforts are being made to improve the quality of maternal and neonatal health (MNH) care. However, progress is impeded by challenges, especially in the area of human resources. All three countries are striving not only to scale up the number of available health staff, but also to improve performance by raising skill levels and enhancing provider motivation. In-depth interviews were used to explore MNH provider views about motivation and incentives at primary care level in rural Burkina Faso, Ghana and Tanzania. Interviews were held with 25 MNH providers, 8 facility and district managers, and 2 policy-makers in each country. Across the three countries some differences were found in the reasons why people became health workers. Commitment to remaining a health worker was generally high. The readiness to remain at a rural facility was far less, although in all settings there were some providers that were willing to stay. In Burkina Faso it appeared to be particularly difficult to recruit female MNH providers to rural areas. There were indications that MNH providers in all the settings sometimes failed to treat their patients well. This was shown to be interlinked with differences in how the term 'motivation' was understood, and in the views held about remuneration and the status of rural health work. Job satisfaction was shown to be quite high, and was particularly linked to community appreciation. With some important exceptions, there was a strong level of agreement regarding the financial and non-financial incentives that were suggested by these providers, but there were clear country preferences as to whether incentives should be for individuals or teams. Understandings of the terms and concepts pertaining to motivation differed between the three countries. The findings from Burkina Faso underline the importance of gender-sensitive health workforce planning. The training that all levels of MNH providers receive in professional ethics, and the way this is reinforced in practice require closer attention. The differences in the findings across the three settings underscore the importance of in-depth country-level research to tailor the development of incentives schemes

Aerosol Delivery of Small Hairpin Osteopontin Blocks Pulmonary Metastasis of Breast Cancer in Mice

Metastasis to the lung may be the final step in the breast cancer-related morbidity. Conventional therapies such as chemotherapy and surgery are somewhat successful, however, metastasis-related breast cancer morbidity remains high. Thus, a novel approach to prevent breast tumor metastasis is needed.Aerosol of lentivirus-based small hairpin osteopontin was delivered into mice with breast cancer twice a week for 1 or 2 months using a nose-only inhalation system. The effects of small hairpin osteopontin on breast cancer metastasis to the lung were evaluated using near infrared imaging as well as diverse molecular techniques. Aerosol-delivered small hairpin osteopontin significantly decreased the expression level of osteopontin and altered the expression of several important metastasis-related proteins in our murine breast cancer model.Aerosol-delivered small hairpin osteopontin blocked breast cancer metastasis. Our results showed that noninvasive targeting of pulmonary osteopontin or other specific genes responsible for cancer metastasis could be used as an effective therapeutic regimen for the treatment of metastatic epithelial tumors