Shikimate kinase: A potential target for development of novel antitubercular agents

Tuberculosis (TB) remains the leading cause of mortality due to a bacterial pathogen, Mycobacterium tuberculosis. However, no new classes of drugs for TB have been developed in the past 30 years. Therefore there is an urgent need to develop faster acting and effective new antitubercular agents, preferably belonging to new structural classes, to better combat TB, including MDR-TB, to shorten the duration of current treatment to improve patient compliance, and to provide effective treatment of latent tuberculosis infection. The enzymes in the shikimate pathway are potential targets for development of a new generation of antitubercular drugs. The shikimate pathway has been shown by disruption of aroK gene to be essential for the Mycobacterium tuberculosis. The shikimate kinase (SK) catalyses the phosphorylation of the 3-hydroxyl group of shikimic acid (shikimate) using ATP as a co-substrate. SK belongs to family of nucleoside monophosphate (NMP) kinases. The enzyme is an alpha/beta protein consisting of a central sheet of five parallel beta-strands flanked by alpha-helices. The shikimate kinases are composed of three domains: Core domain, Lid domain and Shikimate-binding domain. The Lid and Shikimate-binding domains are responsible for large conformational changes during catalysis. More recently, the precise interactions between SK and substrate have been elucidated, showing the binding of shikimate with three charged residues conserved among the SK sequences. The elucidation of interactions between MtSK and their substrates is crucial for the development of a new generation of drugs against tuberculosis through rational drug design.

Product development process: Using real options for assessments and to support the decision-making at decision gates

Enterprises need continuous product development activities to remain competitive in the marketplace. Their product development process (PDP) must manage stakeholders' needs - technical, financial, legal, and environmental aspects, customer requirements, Corporate strategy, etc. -, being a multidisciplinary and strategic issue. An approach to use real option to support the decision-making process at PDP phases in taken. The real option valuation method is often presented as an alternative to the conventional net present value (NPV) approach. It is based on the same principals of financial options: the right to buy or sell financial values (mostly stocks) at a predetermined price, with no obligation to do so. In PDP, a multi-period approach that takes into account the flexibility of, for instance, being able to postpone prototyping and design decisions, waiting for more information about technologies, customer acceptance, funding, etc. In the present article, the state of the art of real options theory is prospected and a model to use the real options in PDP is proposed, so that financial aspects can be properly considered at each project phase of the product development. Conclusion is that such model can provide more robustness to the decisions processes within PDP.

The WIPO development agenda and the contribution of the international library community

Purpose - The purpose of this paper is to analyze the international strengthening of copyright law in developing countries and the active involvement of the international library community in the movement against it.Design/methodology/approach - The paper describes the overprotection of intellectual property rights through international and bilateral treaties, the reaction against such through the proposal of a WIPO development agenda, and the contribution of the international library organizations to the debates and discussions in the WIPO arena.Findings - The initiative for a development agenda for WIPO has proven much more successful than many had imagined, even its promoters. The most relevant proposals made by the international library community were included in the final list of approved recommendations.Originality/value - The paper raises awareness of the relationship between copyright and access to knowledge and, in consequence, the need for library organizations to exert influence in such legislation.

Development of a low-cost mobile mapping system: A South American experience

This paper presents the prototype of a low-cost terrestrial mobile mapping system (MMS) composed of a van, two digital video cameras, two GPS receivers, a notebook computer, and a sound frame synchronisation system. The imaging sensors are mounted as a stereo video camera on top of the vehicle together with the GPS antennae. The GPS receivers and the notebook computer are configured to record data referred to the vehicle position at a planned time interval. This position is subsequently transferred to the road images. This set of equipment and methods provide the opportunity to merge distinct techniques to make topographic maps and also to build georeferenced road image databases. Both vector maps and raster image databases, when integrated appropriately, can give spatial researchers and engineers a new technique whose application may realise better planning and analysis related to the road environment. The experimental results proved that the MMS developed at the São Paulo State University is an effective approach to inspecting road pavements, to map road marks and traffic signs, electric power poles, telephone booths, drain pipes, and many other applications important to people's safety and welfare. A small number of wad images have already been captured by the prototype as a consequence of its application in distinct projects. An efficient organisation of those images and the prompt access to them justify the need for building a georeferenced image database. By expanding it, both at the hardware and software levels, it is possible for engineers to analyse the entire road environment on their office computers.

Chorismate synthase: An attractive target for drug development against orphan diseases

The increase in incidence of infectious diseases worldwide, particularly in developing countries, is worrying. Each year, 14 million people are killed by infectious diseases, mainly HIV/AIDS, respiratory infections, malaria and tuberculosis. Despite the great burden in the poor countries, drug discovery to treat tropical diseases has come to a standstill. There is no interest by the pharmaceutical industry in drug development against the major diseases of the poor countries, since the financial return cannot be guaranteed. This has created an urgent need for new therapeutics to neglected diseases. A possible approach has been the exploitation of the inhibition of unique targets, vital to the pathogen such as the shikimate pathway enzymes, which are present in bacteria, fungi and apicomplexan parasites but are absent in mammals. The chorismate synthase (CS) catalyses the seventh step in this pathway, the conversion of 5-enolpyruvylshikimate-3-phosphate to chorismate. The strict requirement for a reduced flavin mononucleotide and the anti 1,4 elimination are both unusual aspects which make CS reaction unique among flavin-dependent enzymes, representing an important target for the chemotherapeutic agents development. In this review we present the main biochemical features of CS from bacterial and fungal sources and their difference from the apicomplexan CS. The CS mechanisms proposed are discussed and compared with structural data. The CS structures of some organisms are compared and their distinct features analyzed. Some known CS inhibitors are presented and the main characteristics are discussed. The structural and kinetics data reviewed here can be useful for the design of inhibitors. © 2007 Bentham Science Publishers Ltd.

Financing for sustainable development: visions and proposals for action from a Latin American and Caribbean perspective

Foreword Throughout the preparatory process for the World Summit on Sustainable Development and at the Summit itself, which was held in Johannesburg, South Africa, from 26 August to 4 September 2002, discussions were dominated by one central concern: the need to define and reach consensus on concrete, quantitative goals, with fixed deadlines for implementation, which were to supplement the Millennium Development Goals and facilitate progress towards an effective transition to sustainable development. Participants at the Summit explicitly affirmed the need, as a matter of urgency, to identify the financial and technical resources whereby sustainable development would become a reality and benefit directly and particularly rural and urban communities in the developing countries. The document we are now presenting is the outcome of extensive discussions held at a high-level forum during the Johannesburg Summit. Led by representatives of the Government of Mexico, the Economic Commission for Latin America and the Caribbean (ECLAC), the United Nations Development Programme (UNDP) and the Andean Development Corporation, those discussions were based on the ECLAC/UNDP study entitled Financing for sustainable development in Latin America and the Caribbean: from Monterrey to Johannesburg, which considers the opportunities and challenges for improving prospects for investment and financing for sustainable development and underscores the need to establish a new balance between the market economy and public interest through joint public/private initiatives that combine market innovation, social responsibility and appropriate regulations. Other eminent persons attending the event included heads of State, such as Gustavo Noboa, then President of Ecuador; Enrique V. Iglesias, President of the Inter-American Development Bank (IDB); José María Figueres, Managing Director of the Global Agenda of the World Economic Forum and former President of Costa Rica; and Gro Harlem Brundtland, the legendary figure who pioneered sustainable development. Valuable contributions to the discussions were made by Yolanda Kakabadse, President of the World Conservation Union; Xóchitl Gálvez Ruiz, head of the Unit for the Development of Indigenous Peoples of the Office of the President of Mexico; Cecilia López, former Minister for the Environment of Colombia; and Juan Carlos Maqueda, then Vice President of Argentina. The views emerging from the forum as set forth in this document are designed to facilitate and promote application of the Plan of Implementation of the World Summit on Sustainable Development within the framework of the Millennium Development Goals and the commitments assumed at the International Conference on Financing for Development, which was held in Monterrey, Mexico. We also aspire to continue moving forward with the adoption of measures and policies to increase investment and financing for sustainable development as well as to foster partnerships between the public and private sectors and nongovernmental organizations. We recognize, in this context, the importance of strengthening and improving public and private institutions in order to meet the operational needs associated with the effort to achieve the Millennium Development Goals and pursue the Plan of Implementation formulated in Johannesburg. We trust that this document will contribute to in-depth discussions on the application of the Plan of Implementation in the relevant forums, in particular the United Nations Commission on Sustainable Development. The Plan of Implementation of the World Summit on Sustainable Development opens up new opportunities for Latin America and the Caribbean to renew and revive their own regional agenda -with emphasis on global and especially regional public goods- and to interweave it more cohesively with the global agenda in order to promote the common interests of Latin America and the Caribbean more forcefully in international development forums. The regional agenda and the global agenda cannot be separated in a contrived manner; indeed, to an increasing degree, what we are witnessing are global environmental processes which call for action at the local level. The achievement of sustainable development in Latin America and the Caribbean, where the necessary economic, social, environmental and geopolitical conditions are combined, requires a subtle balance between the market economy, the State and the citizen. Such a balance will result in the consolidation of democratic governance in the service of human development. VICENTE FOX President of Mexico JOSÉ ANTONIO OCAMPO Executive Secretary, Economic Commission for Latin America and the Caribbean (ECLAC) ELENA MARTÍNEZ Assistant Aministrator and Regional Director for Latin America and the Caribbean of the United Nations Development Programme (UNDP) ENRIQUE GARCÍA Executive President, Andean Development Corporation (ADC)""

Finance for development: Latin America in comparative perspective

Includes bibliography

The sustainability of development in Latin America and the Caribbean: challenges and opportunities

Includes bibliography

Sustainable development: changing production patterns, social equity and the environment

Includes bibliography

A decade of social development in Latin America, 1990-1999

Includes bibliography

Rethinking the development agenda

Includes bibliography

The millennium development goals: a Latin American and Caribbean perspective

Includes bibliography

Millennium development goals. 2006 report: a look at gender equality and empowerment of women in Latin America and the Caribbean

Includes bibliography

Millennium development goals: progress towards the right to health in Latin america and the Caribbean

Includes bibliography

Proposed regional agenda on population and development for Latin America and the Caribbean beyond 2014

The document revisits, broadens and updates the discussions contained in ECLAC documents Input for the preparation of a regional agenda for the Programme of Action of the International Conference on Population and Development: towards 2014 and beyond (LC/L.3219(CEP.2010/4)), of 2010, and Reflections on the population and development agenda for Latin America and the Caribbean beyond 2014 (LC/L.3481(CEP.2/5)), of 2012..