According to the "membrane sensor" hypothesis, the membrane's physical properties and microdomain organization play an initiating role in the heat shock response. Clinical conditions such as cancer, diabetes and neurodegenerative diseases are all coupled with specific changes in the physical state and lipid composition of cellular membranes and characterized by altered heat shock protein levels in cells suggesting that these "membrane defects" can cause suboptimal hsp-gene expression. Such observations provide a new rationale for the introduction of novel, heat shock protein modulating drug candidates. Intercalating compounds can be used to alter membrane properties and by doing so normalize dysregulated expression of heat shock proteins, resulting in a beneficial therapeutic effect for reversing the pathological impact of disease. The membrane (and lipid) interacting hydroximic acid (HA) derivatives discussed in this review physiologically restore the heat shock protein stress response, creating a new class of "membrane-lipid therapy" pharmaceuticals. The diseases that HA derivatives potentially target are diverse and include, among others, insulin resistance and diabetes, neuropathy, atrial fibrillation, and amyotrophic lateral sclerosis. At a molecular level HA derivatives are broad spectrum, multi-target compounds as they fluidize yet stabilize membranes and remodel their lipid rafts while otherwise acting as PARP inhibitors. The HA derivatives have the potential to ameliorate disparate conditions, whether of acute or chronic nature. Many of these diseases presently are either untreatable or inadequately treated with currently available pharmaceuticals. Ultimately, the HA derivatives promise to play a major role in future pharmacotherapy.
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BACKGROUND: In many genomics projects, numerous lists containing biological identifiers are produced. Often it is useful to see the overlap between different lists, enabling researchers to quickly observe similarities and differences between the data sets they are analyzing. One of the most popular methods to visualize the overlap and differences between data sets is the Venn diagram: a diagram consisting of two or more circles in which each circle corresponds to a data set, and the overlap between the circles corresponds to the overlap between the data sets. Venn diagrams are especially useful when they are 'area-proportional' i.e. the sizes of the circles and the overlaps correspond to the sizes of the data sets. Currently there are no programs available that can create area-proportional Venn diagrams connected to a wide range of biological databases.RESULTS: We designed a web application named BioVenn to summarize the overlap between two or three lists of identifiers, using area-proportional Venn diagrams. The user only needs to input these lists of identifiers in the textboxes and push the submit button. Parameters like colors and text size can be adjusted easily through the web interface. The position of the text can be adjusted by 'drag-and-drop' principle. The output Venn diagram can be shown as an SVG or PNG image embedded in the web application, or as a standalone SVG or PNG image. The latter option is useful for batch queries. Besides the Venn diagram, BioVenn outputs lists of identifiers for each of the resulting subsets. If an identifier is recognized as belonging to one of the supported biological databases, the output is linked to that database. Finally, BioVenn can map Affymetrix and EntrezGene identifiers to Ensembl genes.CONCLUSION: BioVenn is an easy-to-use web application to generate area-proportional Venn diagrams from lists of biological identifiers. It supports a wide range of identifiers from the most used biological databases currently available. Its implementation on the World Wide Web makes it available for use on any computer with internet connection, independent of operating system and without the need to install programs locally. BioVenn is freely accessible at http://www.cmbi.ru.nl/cdd/biovenn/.
