Pathway prioritization

This chapter focuses on a novel antibiotic discovery paradigm. Metallo-hydrolases and Mur ligases are used to illustrate this approach. New methods to identify and prioritize targets, develop screens, and evaluate new inhibitors are discussed. New developments in enzyme-based assays, such as pathway assays, are also presented. This new approach is opening new venues for screening targets that are difficult to screen because substrates are not easily available. 

With the recognition of the special susceptibility of children, it is better to prevent than to treat environmental diseases in children. In developing countries, the most important issue may be to prioritize which exposure reductions will have the greatest overall impact with the limited resources that are available. It is important to identify the exposures that pose the greatest health risks, as well as the sources and pathways for these exposures. This information can then be used to make choices that lead to health benefits for children around the world. 

Recommendation 9-3. An independent systems analysis group should be established by the Department of Energy to identify the impacts of various hydrogen technology pathways, to assess associated cost elements and drivers, to identify key cost and technological gaps, to evaluate the significance of actual research results, and to assist in the prioritization of research and development directions. 

It is necessary to highlight those effects of aerosols and other chemical species on meteorological parameters have many different pathways (such as, direct, indirect and semi-direct effects) and they have to be prioritized and considered in... 

As discussed in the introduction, there are an innumerable numbCT of environmental chemicals for which little or no toxicity information is available and for many others for which it is inadequate. HTS studies could be invaluable at three related areas. First, they could identify those chemicals with the greatest potential toxicity and hazard which would then be prioritized for further testing. Second, they may be able to identify pathways of toxicity. Third, they may be able to identify and quantify metabolic pathways. 

Both tools additionally suffer from the small number of reliable biodegradation studies in which transformation pathways were elucidated in enough detail to serve as training data for rule development and prioritization. Especially when confronted with compounds such as current-use pesticides and pharmaceuticals, both tools are lacking some of the rules necessary to break down these more complex molecular structures. Hopefully this situation will improve in the future since with the implementation of REACH, which requests identification of relevant transformation products for all compounds produced in amounts exceeding 100 t/year, the experimental biodegradation database is expected to grow considerably. 

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