Proviral insertions induce the expression of bone-specific isoforms of PEBP2αA (CBFA1): Evidence for a new myc collaborating oncogene

The til-1 locus was identified as a common retroviral integration site in virus-accelerated lymphomas of CD2-myc transgenic mice. We now show that viral insertions at til-1 lead to transcriptional activation of PEBP2αA (CBFA1), a transcription factor related to the Drosophila segmentation gene product, Runt. Insertions are upstream and in the opposite orientation to the gene and appear to activate a variant promoter that is normally silent in T cells. Activity of this promoter was detected in rodent osteogenic sarcoma cells and primary osteoblasts, implicating bone as the normal site of promoter activity. The isoforms encoded by the activated gene all encompass the conserved runt DNA-binding domain and share a novel N terminus different from the previously reported PEBP2αA products. Minor products include isoforms with internal deletions due to exon skipping and a novel C-terminal domain unrelated to known runt domain factors. The major isoform expressed from the activated til-1 locus (G1) was found to account for virtually all of the core binding factor activity in nuclear extracts from its corresponding lymphoma cell line. Another member of this gene family, AML1(CBFA2), is well known for its involvement in human hemopoietic tumors. These results provide evidence of a direct oncogenic role for PEBP2αA and indicate that the Myc and Runt family genes can cooperate in oncogenesis.

Ancient origin of pathogen recognition specificity conferred by the tomato disease resistance gene Pto

We have investigated the origin of the Pto disease resistance (R) gene that was previously identified in the wild tomato species Lycopersicon pimpinellifolium and isolated by map-based cloning. Pto encodes a serine-threonine protein kinase that specifically recognizes strains of Pseudomonas syringae pv. tomato (Pst) that express the avirulence gene avrPto. We examined an accession of the distantly related wild species Lycopersicon hirsutum var. glabratum that exhibits avrPto-specific resistance to Pst. The Pst resistance of L. hirsutum was introgressed into a susceptible Lycopersicon esculentum background to create the near-isogenic line 96T133-3. Resistance to Pst(avrPto) in 96T133-3 was inherited as a single dominant locus and cosegregated with a restriction fragment length polymorphism detected by the Pto gene. This observation suggested that a member of the Pto gene family confers Pst(avrPto) resistance in this L. hirsutum line. Here we report the cloning and characterization of four members of the Pto family from 96T133-3. One gene (LhirPto) is 97% identical to Pto and encodes a catalytically active protein kinase that elicits a hypersensitive response when coexpressed with avrPto in leaves of Nicotiana benthamiana. In common with the Pto kinase, the LhirPto protein physically interacts with AvrPto and downstream members of the Pto signaling pathway. Our studies indicate that R genes of the protein kinase class may not evolve rapidly in response to pathogen pressure and rather that their ability to recognize specific Avr proteins can be highly conserved.

Activation of Trk neurotrophin receptors in the absence of neurotrophins

Neurotrophins regulate neuronal cell survival and synaptic plasticity through activation of Trk receptor tyrosine kinases. Binding of neurotrophins to Trk receptors results in receptor autophosphorylation and downstream phosphorylation cascades. Here, we describe an approach to use small molecule agonists to transactivate Trk neurotrophin receptors. Activation of TrkA receptors in PC12 cells and TrkB in hippocampal neurons was observed after treatment with adenosine, a neuromodulator that acts through G protein-coupled receptors. These effects were reproduced by using the adenosine agonist CGS 21680 and were counteracted with the antagonist ZM 241385, indicating that this transactivation event by adenosine involves adenosine 2A receptors. The increase in Trk activity could be inhibited by the use of the Src family-specific inhibitor, PP1, or K252a, an inhibitor of Trk receptors. In contrast to other G protein-coupled receptor transactivation events, adenosine used Trk receptor signaling with a longer time course. Moreover, adenosine activated phosphatidylinositol 3-kinase/Akt through a Trk-dependent mechanism that resulted in increased cell survival after nerve growth factor or brain-derived neurotrophic factor withdrawal. Therefore, adenosine acting through the A2A receptors exerts a trophic effect through the engagement of Trk receptors. These results provide an explanation for neuroprotective actions of adenosine through a unique signaling mechanism and raise the possibility that small molecules may be used to elicit neurotrophic effects for the treatment of neurodegenerative diseases.

The Arabidopsis dwarf1 Mutant Is Defective in the Conversion of 24-Methylenecholesterol to Campesterol in Brassinosteroid Biosynthesis1

Since the isolation and characterization of dwarf1-1 (dwf1-1) from a T-DNA insertion mutant population, phenotypically similar mutants, including deetiolated2 (det2), constitutive photomorphogenesis and dwarfism (cpd), brassinosteroid insensitive1 (bri1), and dwf4, have been reported to be defective in either the biosynthesis or the perception of brassinosteroids. We present further characterization of dwf1-1 and additional dwf1 alleles. Feeding tests with brassinosteroid-biosynthetic intermediates revealed that dwf1 can be rescued by 22α-hydroxycampesterol and downstream intermediates in the brassinosteroid pathway. Analysis of the endogenous levels of brassinosteroid intermediates showed that 24-methylenecholesterol in dwf1 accumulates to 12 times the level of the wild type, whereas the level of campesterol is greatly diminished, indicating that the defective step is in C-24 reduction. Furthermore, the deduced amino acid sequence of DWF1 shows significant similarity to a flavin adenine dinucleotide-binding domain conserved in various oxidoreductases, suggesting an enzymatic role for DWF1. In support of this, 7 of 10 dwf1 mutations directly affected the flavin adenine dinucleotide-binding domain. Our molecular characterization of dwf1 alleles, together with our biochemical data, suggest that the biosynthetic defect in dwf1 results in reduced synthesis of bioactive brassinosteroids, causing dwarfism.

Stimulation of phosphatidylinositol 3-kinase by fibroblast growth factor receptors is mediated by coordinated recruitment of multiple docking proteins

The docking protein FRS2 is a major downstream effector that links fibroblast growth factor (FGF) and nerve growth factor receptors with the Ras/mitogen-activated protein kinase signaling cascade. In this report, we demonstrate that FRS2 also plays a pivotal role in FGF-induced recruitment and activation of phosphatidylinositol 3-kinase (PI3-kinase). We demonstrate that tyrosine phosphorylation of FRS2α leads to Grb2-mediated complex formation with the docking protein Gab1 and its tyrosine phosphorylation, resulting in the recruitment and activation of PI3-kinase. Furthermore, Grb2 bound to tyrosine-phosphorylated FRS2 through its SH2 domain interacts primarily via its carboxyl-terminal SH3 domain with a proline-rich region in Gab1 and via its amino-terminal SH3 domain with the nucleotide exchange factor Sos1. Assembly of FRS2α:Grb2:Gab1 complex induced by FGF stimulation results in activation of PI3-kinase and downstream effector proteins such as the S/T kinase Akt, whose cellular localization and activity are regulated by products of PI3-kinase. These experiments reveal a unique mechanism for generation of signal diversity by growth factor-induced coordinated assembly of a multidocking protein complex that can activate the Ras/mitogen-activated protein kinase cascade to induce cell proliferation and differentiation, and PI3-kinase to activate a mediator of a cell survival pathway.

The challenge of contracting for technological information

Contracting to provide technological information (TI) is a significant challenge. TI is an unusual commodity in five ways. (i) TI is difficult to count and value; conventional indicators, such as patents and citations, hardly indicate value. TI is often sold at different prices to different parties. (ii) To value TI, it may be necessary to “give away the secret.” This danger, despite nondisclosure agreements, inhibits efforts to market TI. (iii) To prove its value, TI is often bundled into complete products, such as a computer chip or pharmaceutical product. Efficient exchange, by contrast, would involve merely the raw information. (iv) Sellers’ superior knowledge about TI’s value make buyers wary of overpaying. (v) Inefficient contracts are often designed to secure rents from TI. For example, licensing agreements charge more than marginal cost. These contracting difficulties affect the way TI is produced, encouraging self-reliance. This should be an advantage to large firms. However, small research and development firms spend more per employee than large firms, and nonprofit universities are major producers. Networks of organizational relationships, particularly between universities and industry, are critical in transmitting TI. Implicit barter—money for guidance—is common. Property rights for TI are hard to establish. Patents, quite suitable for better mousetraps, are inadequate for an era when we design better mice. Much TI is not patented, and what is patented sets fuzzy demarcations. New organizational forms are a promising approach to contracting difficulties for TI. Webs of relationships, formal and informal, involving universities, start-up firms, corporate giants, and venture capitalists play a major role in facilitating the production and spread of TI.

Protein-free cell culture on an artificial substrate with covalently immobilized insulin.

Insulin was immobilized on a surface-hydrolyzed poly(methyl methacrylate) film. Chinese hamster ovary cells overexpressing human insulin receptors were cultured on the film in the absence of serum or soluble proteins. Small amounts of immobilized insulin (1-10% of the required amount of free insulin) were sufficient to stimulate cell proliferation. In addition, the maximal mitogenic effect of immobilized insulin was greater than that of free insulin. Immobilized insulin activated the insulin receptor and downstream signaling proteins, and this activation persisted for longer periods than that obtained with free insulin, probably explaining the greater mitogenic effect of the immobilized insulin. Finally the immobilized-insulin film was usable repeatedly without marked loss of activity.

A gestão de empresas de projeto e a sustentabilidade ambiental de edificações.

O projeto é uma etapa importante do empreendimento do subsetor Edificações, pois é o momento em que muitas decisões sobre o seu desempenho e a execução podem ser tomadas. Por essa razão, essa etapa é estratégica em relação à sustentabilidade ambiental. O objetivo geral da presente tese é propor diretrizes de gestão para empresas de projeto com foco no atendimento a requisitos ambientais em projetos de edificações. Para atingir o objetivo proposto, três etapas de pesquisa foram realizadas. A Etapa 1 tem foco no diagnóstico das práticas de algumas empresas que atuam no mercado: empresas de projeto de edificações e de consultoria em sustentabilidade ambiental. Os métodos utilizados nessa etapa são pesquisa-ação, questionário e pesquisa exploratória. Na Etapa 2 da pesquisa, três estudos de caso envolvendo empresas de projeto da cidade de São Paulo foram realizados, a fim de analisar a sua gestão com foco em sustentabilidade ambiental. Na Etapa 3, uma pesquisa survey foi realizada buscando investigar, de modo mais abrangente, se a sustentabilidade ambiental é considerada nos processos gerenciais das empresas. Os principais resultados dos estudos mostram que há fatores externos e internos à empresa que influenciam em sua reação frente às demandas de mercado ou da sociedade; a consideração da sustentabilidade ambiental pela empresa de projeto trouxe mudanças aos seus processos gerenciais. Esses resultados e a literatura fundamentaram a proposição de diretrizes de orientação de gestão para empresas de projeto com foco no atendimento a requisitos ambientais. A gestão propicia um ambiente mais favorável aos conceitos de sustentabilidade, durabilidade e desempenho.

Efetividade dos instrumentos de políticas públicas nos gastos privados de P&D no Brasil

Esse trabalho teve como objetivo contribuir para o debate sobre a importância das políticas de incentivo à inovação no Brasil. Os resultados esperados do uso que as empresas fizeram dos diferentes tipos de instrumentos sobre os gastos em pesquisa e desenvolvimento (P&D) foram avaliados pelo método de diferenças em diferenças. O método permitiu obter as diferenças de gastos entre empresas beneficiárias de instrumentos e as não-beneficiárias em três períodos consecutivos: 2005 em relação à 2003; 2008 em relação à 2005 e de 2011 em relação à 2008. Ao fazer isso, foi possível identificar se tais diferenças foram positivas e significativas, podendo ser atribuídas às influências dos instrumentos. Os instrumentos utilizados foram: incentivos fiscais, Lei de Informática, financiamentos em parcerias, financiamentos sem parcerias e subvenção. E a utilização dos mesmos pelas empresas teve maior relevância no âmbito de diversos programas de apoio à inovação vigentes no país a partir da retomada das políticas industriais e tecnológicas, nos anos 2000. O estudo concluiu que os efeitos positivos e significativos são limitados à determinados grupos tecnológicos e à poucos instrumentos, em geral, de caráter fiscal. Além disso, esses efeitos positivos surgem em apenas um período, sendo que para cada grupo tecnológico foram efetuadas estimativas para três períodos. Também não houve evidências de que os instrumentos financeiros exerçam efeitos significativos sobre as decisões de gastos em pesquisa e desenvolvimento, apesar da maior ênfase dada aos mesmos no período estudado. Os resultados sugerem fraca influência dos mecanismos de apoio à P&D no Brasil sobre o aumento dos gastos privados, apesar dos avanços recentes.

Diretrizes para o estabelecimento de parcerias entre empresas do real estate residencial.

O presente trabalho tem como foco o estudo e análise das alianças estratégicas realizadas entre empresas do setor do real estate, no período entre 2006 e 2010, enfatizando as alianças realizadas entre empresas atuantes predominantemente nas cidades de São Paulo e Rio de Janeiro com empresas atuantes nas regiões Norte e Nordeste do Brasil, cujo objetivo por parte das empresas paulistas foi o espalhamento geográfico. Considerando o volume representativo de alianças estratégicas verificado no setor no período em questão e a geração de resultados dos empreendimentos objetos de tais parcerias inferiores às expectativas estabelecidas, o objetivo do trabalho é a apresentação de um conjunto de diretrizes que possa contribuir para o planejamento, realização e condução de futuras parcerias entre empresas do setor, visando a mitigar dificuldades e a explorar da melhor forma possível os benefícios que as alianças estratégicas podem proporcionar. Para tanto, realizou-se uma pesquisa por meio de um estudo de casos múltiplos abrangendo o estudo de empresas de capital aberto que atuavam predominantemente nas capitais do eixo Rio-São Paulo, empresas atuantes em nível regional no Norte e Nordeste brasileiro que realizaram parcerias com as empresas do Sudeste, além de empresas de consultoria que estiveram envolvidas nas parcerias por meio de prestação de serviços. Tal pesquisa permitiu identificar as principais dificuldades, vantagens e desvantagens decorrentes das parcerias em questão, cujos dados foram analisados e discutidos à luz da revisão bibliográfica, embasando assim o conjunto de diretrizes proposto. As diretrizes apresentadas visam a contribuir com todo o processo que envolve a realização de uma parceria, contemplando desde aspectos de planejamento, gestão até aspectos operacionais e são complementadas por recomendações que somadas às diretrizes podem elevar a probabilidade de êxito das parcerias.

Os efeitos da adoção de práticas de inovação gerencial sobre a flexibilidade organizacional

desenvolvem capacidades dinâmicas. Um tipo de inovação é a inovação gerencial que trata de mudanças na maneira de gerir a empresa. As capacidades dinâmicas são responsáveis pela percepção de oportunidades e ameaças e ajustamento da organização respondendo a elas. Tais capacidades causam o desenvolvimento de flexibilidade. Assim, o objetivo deste trabalho é relacionar a adoção de práticas de inovação gerencial à sua contribuição para o desenvolvimento de capacidades dinâmicas, medidas por meio da flexibilidade. O estudo é importante pela pequena atenção dada aos fatores organizacionais nos estudos de inovação, do pequeno número de pesquisas empíricas sobre capacidades dinâmicas e do desconhecimento dos mecanismos que atuam nessas capacidades. Para atender ao objetivo foi realizada uma pesquisa descritiva com etapas qualitativa e quantitativa. Na etapa qualitativa foram listadas práticas de inovação gerencial encontradas na bibliografia. Um painel de especialistas classificou essas práticas de acordo com os tipos de inovação gerencial. Na etapa quantitativa foi feito um levantamento usando questionário estruturado aplicado online no qual se mediu a adoção das práticas de inovação gerencial e uma escala pré-existente mediu a flexibilidade. A lista de respondentes foi obtida da Brasscom, do prêmio Great Place to Work, do Anuário Informática Hoje e Anuário Telecom. Compuseram a população da pesquisa 343 empresas escolhidas por conveniência. O questionário foi enviado para indivíduos do nível estratégico e foram obtidas respostas de 102 empresas. Os dados foram analisados por meio de estatística descritiva, análise fatorial exploratória e modelagem de equações estruturais. Os resultados mostram que entre as empresas do setor de TIC as práticas de organização do local de trabalho são as mais adotadas, e que as empresas que mais adotam inovação e são mais flexíveis são empresas entre 13 e 21 anos de idade, de capital estrangeiro ou misto, e que atuam também no Exterior. Verificou-se ainda que a flexibilidade estratégica, estrutural e operacional compõem as capacidades dinâmicas que por sua vez são afetadas pela adoção de inovação gerencial, especialmente das práticas de negócio. Para as empresas recomenda-se cuidado na adoção de práticas, para que estas não precisem ser abandonadas causando perda de flexibilidade. Nesse processo a atuação proativa dos gestores contribui para manter o ciclo de inovação gerencial funcionando. Como contribuição para a academia, destaca-se uma maior compreensão de como as capacidades dinâmicas são colocadas em prática e a medida dessa capacidade por meio da flexibilidade. Para pesquisas futuras recomendam-se estudos que identifiquem causas e consequências do abandono de práticas de inovação gerencial e a comprovação do modelo com dados de outros setores. Conclui-se que maior atenção deve ser dada ao estudo da inovação gerencial e seus efeitos sobre as capacidades dinâmicas.

In-House Risk

Over the last thirty years or so, as the number of in-house counsel rose and their role increased in scope and prominence, increased attention has been given the various challenges these lawyers face under the ABA Model Rules of Professional Conduct, from figuring out who is the client the in-house lawyer represents, to navigating conflicts of interest, maintaining independence, and engaging in a multijurisdictional practice of law. Less attention, to date, has been given to business risk assessment, perhaps in part because that function appears to be part of in-house counsel’s role as a business person rather than as a lawyer. Overlooking the role of in-house counsel in assessing risk, however, is a risky proposition, because risk assessment constitutes for some in-house counsel a significant aspect of their role, a role that in turn informs and shapes how in-house counsel perform other more overtly legal tasks. For example, wearing her hat as General Counsel, a lawyer for the entity-client may opine and explain issues of compliance with the law. Wearing her hat as the Chief Legal Officer, however, the same lawyer may now be called upon as a member of business management to participate in the decision whether to comply with the law. After outlining some of the traditional challenges faced by in-house counsel under the Rules, this short essay explores risk assessment by in-house counsel and its impact on their role and function under the Rules. It argues that the key to in-house lawyers’ successful navigation of multiple roles, and, in particular, to their effective assessment of business risk is keen awareness of the various hats they are called upon to wear. Navigating these various roles may not be easy for lawyers, whose training and habits of mind often teach them to zoom in on legal risks to the exclusion of business risks. Indeed, law schools continue to teach law students “to think like a lawyer” and law firms, the historical breeding grounds for in-house counsel positions, in a world of increased specialization master the narrower contemplation of legal questions. Yet the present and future of in-house counsel practice demand of its practitioners the careful and gradual coming to terms, buildup and mastery of business risk analysis skills, alongside the cultivation of traditional legal risk analysis tools.

Factores determinantes de los resultados derivados de las actividades de patrocinio y mecenazgo

El objetivo de este trabajo consiste en analizar los resultados empresariales derivados de las acciones de patrocinio y mecenazgo, así como sus factores determinantes. La metodología aplicada utiliza el event study para estimar los excesos de rentabilidad de las acciones generadas en Bolsa por una muestra de 21 noticias de patrocinio y 37 noticias de mecenazgo, correspondientes a 26 empresas españolas. Adicionalmente se realiza un análisis de regresión para determinar la influencia de ciertas dimensiones (el origen del evento, así como el vínculo entre el evento y la actividad de la empresa) sobre dichas rentabilidades anormales. La aplicación empírica efectuada ha permitido detectar que sólo las acciones de patrocinio generan rentabilidad, siendo sus principales determinantes el tamaño y el vínculo entre el evento financiado y la actividad de la empresa.

The differentiated effects of CSR actions in the service industry

Purpose – The purpose of this study is to attempt to explain why the impact of Corporate Social Responsibility (CSR) initiatives may be different and/or more important in service firms compared to manufacturing firms. CSR is becoming a common strategy, hence its extensive research. Central to it is the analysis of the effect of CSR on a firm’s performance, whose outcome depends on firm-specific and industry-related factors. Design/methodology/approach – The event study methodology is applied to all the 248 companies that have ever traded on the Spanish Stock Market between 1990 and 2007. A regression analysis examines potential different effects of CSR on service and goods firms. Findings – The results show that CSR activities have a positive impact on firm performance that is higher for service firms than for manufacturing firms. Actions related to the environment, responsible labor relationships and good corporate governance are especially important in the service context. Research limitations/implications – This research is focused on shareholders’ performance, but it does not consider other stakeholders, such as real consumer behavior or employees’ commitment and productivity. Practical implications – Service firms are likely to gain from focusing on some CSR activities (environment, employees and good corporate governance) and should use their responsible behavior as a valuable tool for public relations and differentiation in the market. Originality/value – This article is the first attempt to empirically test and explain why the relationship between CSR and firm performance may be different (more positive) for service vs manufacturing firms.

El traductor e intérprete emprendedor: análisis de la supervivencia de las empresas y los empresarios autónomos

This study presents an empirical analysis of the determinants of firm and self-employed survival in the Spanish translation sector. In the midst of a global downturn firm and self-employed survival is a key factor for the progress of the economies and for a better and more stable future. The study presents, first of all, a review of the literature on translation, interpreting, career opportunities, and entrepreneurship, and firm survival. The following empirical analysis explores the combination of variables of human capital, contingency and economic investment that potentially drive translation and interpreting firms or self-employed entrepreneurs to survive. The study performs a comparative qualitative analysis with a fs/QCA methodology identifying nine combination of causes that lead to the outcome. The results contribute towards a better understanding of entrepreneur translators’ lifespan as they provide an empirical outlook on the different causal paths that predict the survival of those translation and interpreting firms or self-employed entrepreneurs. The last part concludes with the most relevant findings of this research study. With little literature on the topic of firm survival in the translation and interpreting sector the paper aims to fill this gap and make a valuable contribution to the current literature on translation-firm creation and firm and self-employed survival.