983 resultados para growth, development and aging
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Thailand's economic cooperation with neighboring countries, including not only trade and investment but also economic assistance, is tied inseparably to regional development within Thailand. Assistance to develop infrastructure along economic corridors, for example, promotes Thai regional development. This study examines the trade and investment relationships between Thailand and its neighboring countries, as well as related economic policies of Thailand. The study also examines the type of economic assistance being extended, and the resulting regional development taking place. And lastly, the study considers policies for further cooperation by Thailand and the implications this has for Japanese economic cooperation.
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In the wake of economic globalization and development in Thailand, movement of people and commodities at the Thai borders is also becoming pronounced. Economic interdependence between Thailand and neighboring countries is growing through border customhouses. As a policy, Thailand is trying to stimulate trade and investment with neighboring countries following the ACMECS (Ayeyawady-Chao Phraya-Mekong Economic Cooperation Strategy) scheme. In this report, first, movement of people and goods at the borders will be examined. Second, clarification of where and how development is proceeding will be presented. Last, this study will attempt to review the perspectives of policies on neighboring countries after Thaksin.
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This paper reveals how rural Cambodian people reconstructed their social relationships after the collapse of the Pol Pot regime by examining farmland, which was the most important means of production in rural areas at that time. Section 1 and 2 illustrate the process of returning from collective farming under the Pol Pot regime to the family farming system. Section 3 analyzes the structure of land ownership created through land distribution by Krom Samakki. Section 4 studies the actualities of tenant farming. Section 5 examines the changes of the land ownership structure during a decade years after the distribution of Krom Samakki. This paper concludes that the legacy of Krom Samakki started to fade as early as the 1990s.
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This paper explores the causal links between the role of public finance and Bihar's growth and development in the last decade; and argues that these links are tenuous. Bihar's growth acceleration precedes the ‘policy reforms' in public finance based on the ‘good governance' agenda initiated since 2005-06. However, the constraints on sustaining efforts to close Bihar's development gap with the rest of India stems from the nature of the growth process in its regional, sectoral and social dimensions and the contradictory means and ends of the ‘policy reforms' in public finance. Together, this has not only prevented the economic growth to add to public coiffeurs of the state but also occluded the role of tax institutions.
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The influence of feed form and energy concentration of the diet on growth performance and the development of the gastrointestinal tract (GIT) was studied in brown-egg laying pullets. Diets formed a 2 x 5 factorial with 2 feed forms (mash vs. crumbles) and 5 levels of energy differing in 50 kcal AMEn/kg. For the entire study (0 to 17 wk of age) feeding crumbles increased ADFI (52.9 vs. 49.7 g; P < 0.001) and ADG (12.7 vs. 11.6 g; P < 0.001) and improved feed conversion ratio (FCR; 4.18 vs. 4.27; P < 0.001). An increase in the energy content of the diet decreased ADFI linearly (P < 0.001) and improved FCR quadratically (P < 0.01) but energy intake (kcal AMEn/d) was not affected. BW uniformity was higher (P < 0.05) in pullets fed crumbles than in those fed mash but was not affected (P > 0.05) by energy content of the diet. At 5, 10, and 17 wk of age, the relative weight (RW, % BW) of the GIT and the gizzard, and gizzard digesta content were lower (P < 0.05 to P < 0.001) and gizzard pH was higher (P < 0.05 to P < 0.001) in pullets fed crumbles than in pullets fed mash. Energy concentration of the diet did not affect any of the GIT variables studied. In summary, feeding crumbles improved pullet performance and reduced the RW of the GIT and gizzard, and increased gizzard pH at all ages. An increase in the energy content of the diet improved FCR from 0 to 17 wk of age. The use of crumbles and the increase in the AMEn content of the diet might be used adventageously when the objetive is to increase the BW of the pullets. However, crumbles affected the development and weight of the organs of the GIT, which might have negative effects on feed intake and egg production at the beginning of the egg laying cycle.
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El panorama global está cambiando, y esto influye sobre la forma en la que entendemos y tratamos de alcanzar un desarrollo humano sostenible. El crecimiento de la población conlleva una mayor presión sobre los recursos, pero también supone una mayor cantidad de mano de obra y de talento; la concentración en áreas urbanas está cambiando las dinámicas sociales y desafiando los canales de comercialización tradicionales, pero también genera nuevos mercados y fomenta la innovación; los cambios en la economía global están reduciendo los tradicionales desequilibrios de poder entre los países occidentales y el resto del mundo; y las crecientes interconexiones crean nuevos riesgos pero también oportunidades para lanzar iniciativas de alcance global. Todas estas tendencias nos están obligando a repensar qué es el desarrollo humano y de qué manera deberíamos afrontar el reto de la pobreza. Es comúnmente aceptado que la globalización implica interdependencia y que, para conseguir un desarrollo humano sostenible, la colaboración entre actores de distintos ámbitos es necesaria. Se observa una creciente convergencia de temas, intereses y soluciones en torno al desarrollo sostenible, incluso en diferentes países y sectores, lo que está facilitando la colaboración estratégica entre empresas, gobiernos y sociedad civil. Existen pocas duda a día de hoy sobre el papel fundamental que las empresas deben desempeñar en la transición mundial hacia la sostenibilidad ambiental y la erradicación de la pobreza. Las empresas están evolucionando desde un enfoque tradicional centrado en la maximización de beneficios económicos hacia un enfoque holístico que integra la sostenibilidad y la responsabilidad social como parte del núcleo de negocio de las compañías. En el ámbito medioambiental, muchas empresas ya han comenzado a actuar y tratan de reducir sus emisiones, sus desechos y su consumo de energía. Sin embargo la contribución de las empresas a la reducción de la pobreza no está tan clara. Actualmente en torno a 1,2 miles de millones de personas viven en situación de extrema pobreza. La mayoría de estas personas aún vive en zonas rurales donde la mayor parte de la población activa trabaja en el sector agrícola. Por lo tanto, mejorar las oportunidades y reducir los riesgos de los productores más vulnerables en el sector de la agricultura puede ser un motor de desarrollo rural y reducción de la pobreza, especialmente en países de bajo nivel de desarrollo cuyas economías están fundamentalmente basadas en la agricultura. Algunas empresas comienzan a incluir a los pobres en sus operaciones como consumidores, proveedores y emprendedores. Esta tesis se centra en las potenciales oportunidades relacionadas con la incorporación sostenible de los pobres como proveedores de productos y/o de mano de obra. La colaboración entre empresas y productores vulnerables de países en desarrollo es un tema relativamente nuevo y todavía poco estudiado. La pregunta que guía esta tesis es: “¿Cómo pueden las empresas facilitar la inclusión sostenible en cadenas de suministro de productores vulnerables de los países menos desarrollados?”. Para responder a la pregunta anterior, la autora ha aplicado una metodología de casos de estudio. Esta metodología se considera apropiada porque la investigación sobre cadenas de suministro inclusivas es todavía escasa y porque es necesario entender en profundidad un fenómeno de la vida real, y para ello es fundamental conocer su contexto. En primer lugar, se realiza una revisión de literatura para identificar las proposiciones y los constructos teóricos que guiarán la posterior recogida de datos. La revisión de literatura se divide en dos partes: una más general que explora la dimensión social de la sostenibilidad en cadenas de suministro, y una más específica que se centra en la incorporación de los pobres como proveedores en cadenas de suministro. A lo largo de la última década, ha habido un crecimiento exponencial de los estudios académicos sobre la sostenibilidad de las cadenas de suministro, pero la mayoría de los esfuerzos se han dirigido hacia la dimensión medioambiental de la sostenibilidad. Por lo tanto la revisión de literatura, que se presenta en la Sección 3.1 (página 35) y que profundiza en la sostenibilidad social de las cadenas de suministro, puede considerarse una contribución en sí misma. Esta revisión de literatura revela que la investigación sobre aspectos sociales en cadenas de suministro está cobrando impulso en distintas áreas de conocimiento, principalmente en los ámbitos de investigación sobre “gestión de cadenas de suministro”, “responsabilidad social corporativa” y “estudios del desarrollo”. La investigación existente sobre sostenibilidad social de cadenas de suministro se centra en tres temas: aclarar la definición de sostenibilidad social; analizar la implementación de estrategias de sostenibilidad social en cadenas de suministro; y estudiar el apoyo de las em presas líderes a proveedores vulnerables para facilitar su transición hacia la sostenibilidad. Un marco conceptual que resume los principales hallazgos de esta primera parte de la revisión de literatura es planteado en la Figura 7 (página 48). No obstante, en el área de investigación que está emergiendo en torno a la sostenibilidad social de las cadenas de suministro, los estudios relacionados con la reducción de la pobreza son aún escasos. Además se aprecia una falta de contribuciones desde y sobre los países menos desarrollados, así como una clara tendencia a reflejar la visión de las empresas líderes de las cadenas de suministro, olvidando la perspectiva de los proveedores. La segunda parte de la revisión de literatura presentada en la Sección 3.2 (página 51) profundiza en tres líneas de investigación que exploran, desde distintas perspectivas, la inclusión de los pobres en cadenas de suministro. Estas líneas son “Global Value Chains” (GVC), “Base of the Pyramid” (BoP) y “Sustainable Supply Chain Management” (SSCM). La investigación en GVC analiza las cadenas de suministro desde la perspectiva de la globalización económica y el comercio internacional, poniendo especial énfasis en las implicaciones para los países en desarrollo y las comunidades vulnerables. GVC caracteriza las cadenas de suministro según la forma en la que son gobernadas, las oportunidades de mejora que existen para los productores que forman parte de la cadena y el grado de inclusión o exclusión de las comunidades más pobres y vulnerables. La investigación en BoP explora las relaciones comerciales entre empresas y comunidades pobres. La premisa fundamental del concepto BoP es la posibilidad de combinar la generación de beneficios con la reducción de la pobreza. La propuesta original es que mediante la venta de productos y servicios a las comunidades pobres de países en desarrollo, la pobreza puede ser reducida al tiempo que las empresas incrementan sus beneficios, especialmente las grandes empresas multinacionales. Esta idea ha ido evolucionando y, a día de hoy, los investigadores BoP consideran la incorporación de los pobres no sólo como consumidores sino también como empleados, proveedores y co-creadores. La investigación en SSCM ha estado fundamentalmente orientada al estudio de la dimensión medioambiental de la sostenibilidad de cadenas de suministro. Sin embargo, la creciente externalización de la producción a países en desarrollo y las demandas de los grupos de interés para que las empresas aborden todos los aspectos de la sostenibilidad han llevado a los académicos de SSCM a reconocer la importancia de integrar asuntos relacionados con la reducción de la pobreza en sus investigaciones. Algunos estudios comienzan a apuntar los principales retos a los que se enfrentan las empresas para colaborar con productores vulnerables en sus cadenas de suministro. Estos retos son: falta de comunicación, altos costes de transacción y el incremento de la complejidad de las operaciones. Las contribuciones de estas tres líneas de investigación son complementarias para el estudio de las cadenas de suministro inclusivas. Sin embargo, raramente han sido consideradas conjuntamente, ya que pertenecen a ámbitos de conocimiento distintos. Esta tesis integra las aportaciones de GVC, BoP y SSCM en un marco conceptual para la creación y gestión de cadenas de suministro inclusivas. Este marco conceptual para cadenas de suministro inclusivas queda representado en la Figura 9 (página 68). El marco conceptual refleja las motivaciones que llevan a las empresas a colaborar con productores vulnerables, los retos a los que se enfrentan al hacerlo, y los caminos o estrategias que están siguiendo para construir y operar cadenas de suministro inclusivas de manera que sean beneficiosas tanto para la empresa como para los productores vulnerables. A fin de validar y refinar el marco conceptual propuesto, tres casos de estudio se llevan a cabo. Las cadenas de suministro analizadas por los casos de estudio pertenecen al sector agrícola y sus principales proveedores se encuentran en países de África subsahariana. Múltiples métodos de recolección de datos y triangulación son utilizados para mejorar la fiabilidad de los datos. La autora desarrolló trabajos de campo en Senegal, Etiopía y Tanzania. Estos viajes permitieron enriquecer el proceso de recogida de información mediante entrevistas semiestructuradas y conversaciones informales con los principales actores de la cadena de suministro y mediante la observación directa de los procesos y las interacciones entre productores vulnerables y empresas. El Caso de estudio A (Sección 5.1 en página 96) es un caso de estudio único. Analiza la cadena de suministro local de verduras en Senegal. La organización focal es Manobi, una empresa senegalesa que provee servicios de bajo coste a emprendedores locales del sector agrícola. El Caso de estudio A proporciona un interesante análisis del funcionamiento de una cadena de suministro local en un país en desarrollo y muestra como la provisión de servicios profesionales puede mejorar el desempeño de productores vulnerables. El Caso de estudio B (Sección 5.2 en página 122) es un caso de estudio único. Analiza la cadena de suministro global de flor cortada con origen en Etiopía. La organización focal es EHPEA, la Asociación Etíope de Productores y Exportadores Hortícolas, cuya misión es promover y salvaguardar la posición competitiva del sector agrícola etíope en el mercado global. El Caso de estudio B ayuda a comprender mejor la perspectiva de los proveedores respecto a los requerimiento de sostenibilidad del mercado global. También muestra cómo la inclusión de los productores en el proceso de desarrollo de un estándar privado facilita su implementación posterior. El Caso de estudio C (Sección 5.3 en página 143) es un caso de estudio múltiple. Analiza la cadena de suministro global de café especial con origen en Tanzania. Las organizaciones focales son comerciantes que conectan de manera directa a pequeños agricultores de café en países en desarrollo con empresas tostadoras de café en países desarrollados. El Caso de estudio C muestra cómo un pequeño agricultor puede proveer un producto “premium” al mercado global, y participar en un segmento diferenciado del mercado a través de una cadena de suministro transparente y eficiente. Las aportaciones empíricas de los casos de estudio ayudan a validar y mejorar el marco conceptual sobre cadenas de suministro inclusivas (ver discusión en el Capítulo 6 en página 170). El resultado es la propuesta de una nueva versión del marco conceptual representado en la Figura 40 (página 195). Los casos de estudio también proporcionan interesantes aportaciones en relación a la gestión de cadenas de suministro inclusivas y muestran las perspectivas de distintos actores implicados. Esta tesis arroja luz sobre el papel de las empresas en la creación y la gestión de cadenas de suministro inclusivas llevando a cabo una revisión de literatura multidisciplinar y analizando tres casos de estudio en países africanos. Como resultado, esta tesis presenta una serie de contribuciones empíricas y teóricas al ámbito de investigación emergente en torno a las cadenas de suministro inclusivas (Capítulo 7). Esta tesis también pretende ser útil a profesionales que deseen facilitar la incorporación de los pobres como proveedores en condiciones justas y beneficiosas. ABSTRACT The global outlook is changing, and this is influencing the way we understand and try to achieve sustainable human development. Population growth entails increasing pressure over resources, but it also provides greater workforce and talent; concentration in urban areas is changing social dynamics and challenging traditional marketing channels, but also creating news markets and driving innovation; the global economy shift is rebalancing the traditional power imbalance between Western countries and the rest of the world, making new opportunities to arise; and interconnections and global interdependence create new risks but also opportunities for launching initiatives with a global reach. All these trends are impelling us to rethink what development is and in which way poverty alleviation should be approached. It is generally agreed that globalization implies interdependence and, in order to achieve sustainable human development, collaboration of all actors is needed. A convergence of issues, interests and solutions related to sustainable development is being observed across countries and sectors, encouraging strategic collaboration among companies, governments and civil society. There is little doubt nowadays about the crucial role of the private sector in the world’s path towards environmental sustainability and poverty alleviation. Businesses are evolving from a “business as usual” stance to a more sustainable and responsible approach. In the environmental arena, many companies have already “walk the talk”, implementing environmental management systems and trying to reduce emissions and energy consumption. However, regarding poverty alleviation, their contribution is less clear. There are around 1.2 billion people living in extreme poverty. Most of this people still live in rural areas where the agricultural sector employs a big part of the active population. Therefore, improving opportunities and reducing risks for vulnerable producers in the agri-food sector can be a primary engine of rural development and poverty alleviation, particularly in the poor, agriculture-based economies of least developed countries. Some companies are beginning to include the poor into their operations as consumers, suppliers and entrepreneurs. This thesis focuses specifically on the potential opportunities related to the sustainable incorporation of the poor as suppliers of products and/or labor. Business collaboration with vulnerable producers in developing countries is a relatively new trend and it is still understudied. The overall question guiding this thesis is: “How can businesses facilitate the sustainable inclusion of vulnerable producers from least developed countries into supply chains?”. In order to answer the research question, the author has applied a case study research strategy. This methodology is considered appropriate because research about inclusive supply chains is still at an early stage, and because there is a need to understand a real-life phenomenon in depth, but such understanding encompasses important contextual conditions. First, a literature review is conducted, in order to identify the research propositions and theoretical constructs that will guide the data collection. The literature review is divided in two parts: a more general one that explores the social dimension of sustainability of supply chains, and a more specific one that focuses on the incorporation of the poor as suppliers in supply chains. During the last decade, there has been an exponential growth of studies in the field of supply chain sustainability, but research efforts have traditionally been directed towards the analysis of the environmental dimension. Therefore, the literature review presented in Section 3.1 (page 35) that delves into social sustainability of supply chains can be considered a contribution in itself. This literature review reveals that the investigation of social issues in supply chains is gaining momentum and comes from different academic disciplines, namely Supply Chain Management, Corporate Social Responsibility and Development Studies. Existing research about social sustainability of supply chains focuses on three issues: clarify the definition of social sustainability; analyze the implementation of social sustainability strategies in supply chains; and study lead companies’ support to vulnerable suppliers in their transition towards sustainability. A conceptual framework that outlines the main findings that emerge from this first part of literature review is proposed in Figure 7 (page 48). Nevertheless, in this nascent field of social sustainability of supply chains, studies related to poverty alleviation are still scarce. Moreover, a lack of contributions from and about least developed countries has been observed, as well as a tendency to reflect on the lead firms’ standpoint, neglecting the suppliers’ perspective. The second part of the literature review (Section 3.2 in page 51) delves into three research streams that are exploring the inclusion of the poor into supply chains from different viewpoints. These research streams are Global Value Chains (GVC), Base of the Pyramid (BoP) and Sustainable Supply Chain Management (SSCM). GVC research discusses the dynamics of economic globalization and international trade, putting special emphasis in the implications for developing countries and vulnerable communities. GVC characterizes supply chains by the way they are governed, the upgrading opportunities that exist for producers in the chain and the degree of inclusion or exclusion of impoverished communities. BoP research explores trading relationships between businesses and impoverished communities. The core premise of the BoP concept is the possibility to combine profits with poverty alleviation. The original BoP proposition is that by marketing innovative products and services to poor communities in developing countries, poverty would be reduced and companies would increase their benefits, especially multinational companies. This idea has evolved to consider the incorporation of the poor to business activities not only as consumers, but also as employees, entrepreneurs and co-creators. The SSCM school of thought has mainly focused on studying the environmental dimension of supply chain sustainability, neglecting the consideration of the social perspective. However, in recent years, increasing outsourcing of production to developing countries and stakeholders’ demands for a more holistic approach to business sustainability have led SSCM scholars to acknowledge the importance of integrating poverty concerns in this field’s research agenda. Some SSCM studies identify the main operational challenges for companies which engage with vulnerable suppliers in their supply chains: missing communication, higher transactional and operational costs and increased complexity. Contributions from these three research streams are complementary for the study of inclusive supply chains. However, they have been rarely considered together, since they belong to different research areas. This thesis seeks to play a dovetailing role in this scenario by proposing a conceptual framework for creating and operating inclusive supply chains that builds on contributions from GVC, SSCM and BoP research. This framework for inclusive supply chains is depicted in Figure 9 (page 68), and explains the motivations that drive businesses to collaborate with vulnerable suppliers, the chal lenges they face in doing so, and the pathways they are following in order to build and operate inclusive supply chains profitably for both buying companies and vulnerable suppliers. In order to validate and refine the proposed framework, three case studies are carried out. The supply chains analyzed by the case studies belong to the agri-food sector and source from Sub-Saharan African countries. Multiple data collection methods and triangulation are used in order to improve reliability of findings. The author carried out field work in Senegal, Ethiopia and Tanzania. These travels enriched the data collection process, providing semi-structured interviews and informal conversations with the main actors in the supply chains, as well as direct observation of processes and interactions among companies and vulnerable suppliers. Case study A (Section 5.1 in page 96) is a single case study. It analyzes a local supply chain in Senegal providing vegetables to the local market. The focal organization is Manobi, a Senegalese inclusive business which provides affordable ICT services to local entrepreneurs in the agri-food sector. Case study A provides interesting insights into the dynamics of local supply chains and how professional services can help to improve their performance. Case study B (Section 5.2 in page 122) is a single case study. It analyzes a global supply chain with origin in Ethiopia providing cut flowers to the global commodity market. The focal organization is EHPEA, Ethiopian Horticulture Producers and Exporters Association, whose mission is to promote and safeguard the competitive position of the Ethiopian horticulture sector within the global market. Case study B helps to better understand the suppliers’ perspective regarding global market sustainability requirements and shows how the inclusion of suppliers in the process of development of a private standard has a positive impact in its implementation. Case study C (Section 5.3 in page 143) is a multiple case study. It analyzes a global supply chain with origin in Tanzania providing coffee to the global niche market of specialty coffee. The focal organizations are traders who are directly connecting smallholder coffee farmers in developing countries to coffee roasters in developed countries. Case study C shows how smallholder farmers can supply a premium product and be incorporated in a differentiated market segment through a transparent and efficient supply chain. The empirical findings from the case studies help to validate and refine the conceptual framework (see discussion in Chapter 6). The proposal of a new version of the conceptual framework is depicted in Figure 40 (page 195). The case studies also provide interesting insights related to the management of inclusive supply chains and show the perspectives of the different actors involved. This thesis sheds some light on the role of businesses in the creation and operation of inclusive supply chains by carrying out a cross-disciplinary literature review and analyzing three case studies in African countries. In doing so, this thesis presents a series of theoretical and empirical contributions to the emerging academic field of inclusive supply chains (Chapter 7). This thesis also intends to be useful to practitioners willing to improve the incorporation of the poor as suppliers in fair and profitable conditions.
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Skeletal formation is a fundamental element of body patterning and is strictly regulated both temporally and spatially by a variety of molecules. Among these, retinoic acid (RA) has been shown to be involved in normal skeletal development. However, its pleiotropic effects have caused difficulty in identifying its crucial target cells and molecular mechanisms for each effect. Development of cartilage primordia is an important process in defining the skeletal structures. To address the role of RA in skeletal formation, we have generated mice expressing a dominant-negative retinoic acid receptor (RAR) in chondrogenic cells by using the type II collagen α1 promoter, and we have analyzed their phenotypes. These mice exhibited small cartilage primordia during development and retarded skeletal formation in both embryonic and postnatal periods. They also showed selective degeneration in their cervical vertebrae combined with homeotic transformations, but not in their extremities. The cervical phenotypes are reminiscent of phenotypes involving homeobox genes. We found that the expression of Hoxa-4 was indeed reduced in the cartilage primordia of cervical vertebrae of embryonic day 12.5 embryos. These observations demonstrate that endogenous RA acts directly on chondrogenic cells to promote skeletal growth in both embryonic and growing periods, and it regulates the proper formation of cervical vertebrae. Furthermore, RA apparently specifies the identities of the cervical vertebrae through the regulation of homeobox genes in the chondrogenic cells. Great similarities of the phenotypes between our mice and reported RAR knockout mice revealed that chondrogenic cells are a principal RA target during complex cascades of skeletal development.
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The signal transducer and activator of transcription, STAT5b, has been implicated in signal transduction pathways for a number of cytokines and growth factors, including growth hormone (GH). Pulsatile but not continuous GH exposure activates liver STAT5b by tyrosine phosphorylation, leading to dimerization, nuclear translocation, and transcriptional activation of the STAT, which is proposed to play a key role in regulating the sexual dimorphism of liver gene expression induced by pulsatile plasma GH. We have evaluated the importance of STAT5b for the physiological effects of GH pulses using a mouse gene knockout model. STAT5b gene disruption led to a major loss of multiple, sexually differentiated responses associated with the sexually dimorphic pattern of pituitary GH secretion. Male-characteristic body growth rates and male-specific liver gene expression were decreased to wild-type female levels in STAT5b−/− males, while female-predominant liver gene products were increased to a level intermediate between wild-type male and female levels. Although these responses are similar to those observed in GH-deficient Little mice, STAT5b−/− mice are not GH-deficient, suggesting that they may be GH pulse-resistant. Indeed, the dwarfism, elevated plasma GH, low plasma insulin-like growth factor I, and development of obesity seen in STAT5b−/− mice are all characteristics of Laron-type dwarfism, a human GH-resistance disease generally associated with a defective GH receptor. The requirement of STAT5b to maintain sexual dimorphism of body growth rates and liver gene expression suggests that STAT5b may be the major, if not the sole, STAT protein that mediates the sexually dimorphic effects of GH pulses in liver and perhaps other target tissues. STAT5b thus has unique physiological functions for which, surprisingly, the highly homologous STAT5a is unable to substitute.
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Members of the transforming growth factor β (TGF-β) superfamily are involved in diverse physiological activities including development, tissue repair, hormone regulation, bone formation, cell growth, and differentiation. At the cellular level, these functions are initiated by the interaction of ligands with specific transmembrane receptors with intrinsic serine/threonine kinase activity. The signaling pathway that links receptor activation to the transcriptional regulation of the target genes is largely unknown. Recent work in Drosophila and Xenopus signaling suggested that Mad (Mothers against dpp) functions downstream of the receptors of the TGF-β family. Mammalian Mad1 has been reported to respond to bone morphogenetic protein (BMP), but not to TGF-β or activin. We report here the cloning and functional studies of a novel mammalian Mad molecule, Mad3, as well as a rat Mad1 homologue. Overexpression of Mad3 in a variety of cells stimulated basal transcriptional activity of the TGF-β/activin-responsive reporter construct, p3TP-Lux. Furthermore, expression of Mad3 could potentiate the TGF-β- and activin-induced transcriptional stimulation of p3TP-Lux. By contrast, overexpression of Mad1 inhibited the basal as well as the TGF-β/activin induced p3TP-Lux activity. These findings, therefore, support the hypothesis that Mad3 may serve as a mediator linking TGF-β/activin receptors to transcriptional regulation.
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The c-Abl tyrosine kinase and the p53 tumor suppressor protein interact functionally and biochemically in cellular genotoxic stress response pathways and are implicated as downstream mediators of ATM (ataxia-telangiectasia mutated). This fact led us to study genetic interactions in vivo between c-Abl and p53 by examining the phenotype of mice and cells deficient in both proteins. c-Abl-null mice show high neonatal mortality and decreased B lymphocytes, whereas p53-null mice are prone to tumor development. Surprisingly, mice doubly deficient in both c-Abl and p53 are not viable, suggesting that c-Abl and p53 together contribute to an essential function required for normal development. Fibroblasts lacking both c-Abl and p53 were similar to fibroblasts deficient in p53 alone, showing loss of the G1/S cell-cycle checkpoint and similar clonogenic survival after ionizing radiation. Fibroblasts deficient in both c-Abl and p53 show reduced growth in culture, as manifested by reduction in the rate of proliferation, saturation density, and colony formation, compared with fibroblasts lacking p53 alone. This defect could be restored by reconstitution of c-Abl expression. Taken together, these results indicate that the ATM phenotype cannot be explained solely by loss of c-Abl and p53 and that c-Abl contributes to enhanced proliferation of p53-deficient cells. Inhibition of c-Abl function may be a therapeutic strategy to target p53-deficient cells selectively.
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The transforming growth factor-β (TGFβ) and Wnt/wingless pathways play pivotal roles in tissue specification during development. Activation of Smads, the effectors of TGFβ superfamily signals, results in Smad translocation from the cytoplasm into the nucleus where they act as transcriptional comodulators to regulate target gene expression. Wnt/wingless signals are mediated by the DNA-binding HMG box transcription factors lymphoid enhancer binding factor 1/T cell-specific factor (LEF1/TCF) and their coactivator β-catenin. Herein, we show that Smad3 physically interacts with the HMG box domain of LEF1 and that TGFβ and Wnt pathways synergize to activate transcription of the Xenopus homeobox gene twin (Xtwn). Disruption of specific Smad and LEF1/TCF DNA-binding sites in the promoter abrogates synergistic activation of the promoter. Consistent with this observation, introduction of Smad sites into a TGFβ-insensitive LEF1/TCF target gene confers cooperative TGFβ and Wnt responsiveness to the promoter. Furthermore, we demonstrate that TGFβ-dependent activation of LEF1/TCF target genes can occur in the absence of β-catenin binding to LEF1/TCF and requires both Smad and LEF1/TCF DNA-binding sites in the Xtwn promoter. Thus, our results show that TGFβ and Wnt signaling pathways can independently or cooperatively regulate LEF1/TCF target genes and suggest a model for how these pathways can synergistically activate target genes.
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The effects of ultraviolet-B (UV-B) radiation on water relations, leaf development, and gas-exchange characteristics in pea (Pisum sativum L. cv Meteor) plants subjected to drought were investigated. Plants grown throughout their development under a high irradiance of UV-B radiation (0.63 W m−2) were compared with those grown without UV-B radiation, and after 12 d one-half of the plants were subjected to 24 d of drought that resulted in mild water stress. UV-B radiation resulted in a decrease of adaxial stomatal conductance by approximately 65%, increasing stomatal limitation of CO2 uptake by 10 to 15%. However, there was no loss of mesophyll light-saturated photosynthetic activity. Growth in UV-B radiation resulted in large reductions of leaf area and plant biomass, which were associated with a decline in leaf cell numbers and cell division. UV-B radiation also inhibited epidermal cell expansion of the exposed surface of leaves. There was an interaction between UV-B radiation and drought treatments: UV-B radiation both delayed and reduced the severity of drought stress through reductions in plant water-loss rates, stomatal conductance, and leaf area.
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Endosperm development in Zea mays is characterized by a period of intense mitotic activity followed by a period in which mitosis is essentially eliminated and the cell cycle becomes one of alternating S and G phases, leading to endoreduplication of the nuclear DNA. The endosperm represents a significant contribution to the grain yield of maize; thus, methods that facilitate the study of cellular kinetics may be useful in discerning cellular and molecular components of grain yield. Two mathematical models have been developed to describe the kinetics of endosperm growth. The first describes the kinetics of mitosis during endosperm development; the second describes the kinetics of DNA endoreduplication during endosperm development. The mitotic model is a modification of standard growth curves. The endoreduplication model is composed of six differential equations that represent the progression of nuclei from one DNA content to another during the endoreduplication process. Total nuclei number per endosperm and the number of 3C, 6C, 12C, 24C, 48C, and 96C nuclei per endosperm (C is the haploid DNA content per nucleus) for inbred W64A from 8 to 18 days after pollination were determined by flow cytometry. The results indicate that the change in number of nuclei expressed as a function of the number of days after pollination is the same from one yearly crop to another. These data were used in the model to determine the endosperm growth rate, the maximum nuclei number per endosperm, and transition rates from one C value to the next higher C value. The kinetics of endosperm development are reasonably well represented by the models. Thus, the models provide a means to quantify the complex pattern of endosperm development.
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Jasmonic acid (JA) is a naturally occurring growth regulator found in higher plants. Several physiological roles have been described for this compound (or a related compound, methyl jasmonate) during plant development and in response to biotic and abiotic stress. To accurately determine JA levels in plant tissue, we have synthesized JA containing 13C for use as an internal standard with an isotopic composition of [225]:[224] 0.98:0.02 compared with [225]:[224] 0.15:0.85 for natural material. GC analysis (flame ionization detection and MS) indicate that the internal standard is composed of 92% 2-(+/-)-[13C]JA and 8% 2-(+/-)-7-iso-[13C]JA. In soybean plants, JA levels were highest in young leaves, flowers, and fruit (highest in the pericarp). In soybean seeds and seedlings, JA levels were highest in the youngest organs including the hypocotyl hook, plumule, and 12-h axis. In soybean leaves that had been dehydrated to cause a 15% decrease in fresh weight, JA levels increased approximately 5-fold within 2 h and declined to approximately control levels by 4 h. In contrast, a lag time of 1-2 h occurred before abscisic acid accumulation reached a maximum. These results will be discussed in the context of multiple pathways for JA biosynthesis and the role of JA in plant development and responses to environmental signals.
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Cities, more particularly ‘smart’ cities, could become a catalyst for economic and social development. For this to happen, Europe will need a new type of integrated infrastructure, a new urban governance and policy structure, as well as new finance and business models. Successful smart projects will eventually develop into new business models and companies. While the European Commission cannot mandate or regulate this top down, it has a role to play in nurturing new initiatives to allow Europe the possibility of developing its own Google and Apple.