Relationship between global structural parameters and Enzyme Commission hierarchy: Implications for function prediction

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Relationship between global structural parameters and Enzyme Commission hierarchy: Implications for function prediction

In protein databases there is a substantial number of proteins structurally determined but without function annotation. Understanding the relationship between function and structure can be useful to predict function on a large scale. We have analyzed the similarities in global physicochemical parameters for a set of enzymes which were classified according to the four Enzyme Commission (EC) hierarchical levels. Using relevance theory we introduced a distance between proteins in the space of physicochemical characteristics. This was done by minimizing a cost function of the metric tensor built to reflect the EC classification system. Using an unsupervised clustering method on a set of 1025 enzymes, we obtained no relevant clustering formation compatible with EC classification. The distance distributions between enzymes from the same EC group and from different EC groups were compared by histograms. Such analysis was also performed using sequence alignment similarity as a distance. Our results suggest that global structure parameters are not sufficient to segregate enzymes according to EC hierarchy. This indicates that features essential for function are rather local than global. Consequently, methods for predicting function based on global attributes should not obtain high accuracy in main EC classes prediction without relying on similarities between enzymes from training and validation datasets. Furthermore, these results are consistent with a substantial number of studies suggesting that function evolves fundamentally by recruitment, i.e., a same protein motif or fold can be used to perform different enzymatic functions and a few specific amino acids (AAs) are actually responsible for enzyme activity. These essential amino acids should belong to active sites and an effective method for predicting function should be able to recognize them. (C) 2012 Elsevier Ltd. All rights reserved.

Academic cooperation to foster research and advocacy competences in the occupied Palestinian territory (West Bank)

Palestinians living in the West Bank, a territory occupied by the State of Israel according to International Law, face deprived access to land and a limited ability to move freely which pertains to the presence of Israeli settlements and other infrastructure (closures, restricted or forbidden roads, etc.). This confinement has significant impacts on their economic and social livelihoods, and it is even worsening with the on-going construction of a 709 km long Barrier which mainly runs inside the West Bank. With regard to this situation, there is a clear need to strengthen the capacity of civil society and its representatives to apply sound research processes as a basis for improved advocacy for Palestinian human rights. Monitoring processes and tools are needed to assess the impacts of the Palestinians’ confinement, particularly in relation to the Barrier’s construction. Reliable data has also to be collected, managed, and above all, shared. These challenges have been addressed within the Academic Cooperation Palestine Project (ACPP) that brings together academic partners from the occupied Palestinian territory (oPt) West Bank (WB), and Switzerland as well as other international academic institutions and Palestinian governmental and non-governmental agencies. ACPP started in early 2011 and is designed as a large cooperation networking platform involving researchers, students, public servants and experts from the oPt WB. A large set of actions have already been developed during the first year of the project, including courses, training, and research actions. First relevant results and impacts of the different actions are presented in this paper. Taken as a whole, the project produces valuable results for all partners: useful advocacy material for the Palestinian partners, and a unique “real-scale laboratory” where investigations are jointly conducted to develop novel confinement and change indicators.

Comment on Rule 14a-8(i)(9), Securities and Exchange Commission, June 30, 2015

The Securities and Exchange Commission has been analyzing its interpretation under Subsection (i)(9) of Rule 14a-8. This provision allows for the exclusion of shareholder proposals that conflict with those submitted by management. The staff has been examining its interpretation since instructed to do so by the chair of the SEC following a no action appeal in a case involving Whole Foods. A number of letters and memos submitted in connection with the review have analyzed the issue. At least one asserted that any change in interpretation required the Commission to go through the process of notice and comment. This letter asserts that notice and comment is not required, relying extensively on Perez v. Mortgage Bankers Association.

Chicago, Illinois, railroads and industry, 1886 (Image 2 of 2) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Railway terminal and industrial map of Chicago : showing the termini, connections, and general system by which interchanges and transfers of freights are effected between all railroads centering in and about Chicago, also indicating the location of freight and passenger depots, elevators, warehouses, coal, ore, and other docks, and the leading manufactories, with an alphabetical list of the principle industries located along the lines of the same, drawn & engraved by A. Zecse & Co. It was published by Industrial World. Co. in 1886. Scale [ca. 1:19,300]. This layer is image 2 of 2 total images of the two sheet source map, representing the southern portion of the map. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Illinois East State Plane Coordinate System NAD83 (in Feet) (Fipszone 1201). All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, railroads, drainage, selected buildings and industry locations (e.g. mills, factories, etc.), and more. Includes index of principal industries. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

Chicago, Illinois, railroads and industry, 1886 (Image 1 of 2) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Railway terminal and industrial map of Chicago : showing the termini, connections, and general system by which interchanges and transfers of freights are effected between all railroads centering in and about Chicago, also indicating the location of freight and passenger depots, elevators, warehouses, coal, ore, and other docks, and the leading manufactories, with an alphabetical list of the principle industries located along the lines of the same, drawn & engraved by A. Zecse & Co. It was published by Industrial World. Co. in 1886. Scale [ca. 1:19,300]. This layer is image 1 of 2 total images of the two sheet source map, representing the northern portion of the map. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Illinois East State Plane Coordinate System NAD83 (in Feet) (Fipszone 1201). All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, railroads, drainage, selected buildings and industry locations (e.g. mills, factories, etc.), and more. Includes index of principal industries. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.