With the rapid accumulation of our knowledge on diseases, disease-related genes and drug targets, network-based analysis plays an increasingly important role in systems biology, systems pharmacology and translational science. The new release of VisANT aims to provide new functions to facilitate the convenient network analysis of diseases, therapies, genes and drugs. With improved understanding of the mechanisms of complex diseases and drug actions through network analysis, novel drug methods (e.g., drug repositioning, multi-target drug and combination therapy) can be designed. More specifically, the new update includes (i) integrated search and navigation of disease and drug hierarchies; (ii) integrated disease–gene, therapy–drug and drug–target association to aid the network construction and filtering; (iii) annotation of genes/drugs using disease/therapy information; (iv) prediction of associated diseases/therapies for a given set of genes/drugs using enrichment analysis; (v) network transformation to support construction of versatile network of drugs, genes, diseases and therapies; (vi) enhanced user interface using docking windows to allow easy customization of node and edge properties with build-in legend node to distinguish different node type. VisANT is freely available at: http://visant.bu.edu.

Experimental data exists for only a vanishingly small fraction of sequenced microbial genes. This community page discusses the progress made by the COMBREX project to address this important issue using both computational and experimental resources.

The COMBREX database (COMBREX-DB; combrex.bu.edu) is an online repository of information related to (i) experimentally determined protein function, (ii) predicted protein function, (iii) relationships among proteins of unknown function and various types of experimental data, including molecular function, protein structure, and associated phenotypes. The database was created as part of the novel COMBREX (COMputational BRidges to EXperiments) effort aimed at accelerating the rate of gene function validation. It currently holds information on ∼3.3 million known and predicted proteins from over 1000 completely sequenced bacterial and archaeal genomes. The database also contains a prototype recommendation system for helping users identify those proteins whose experimental determination of function would be most informative for predicting function for other proteins within protein families. The emphasis on documenting experimental evidence for function predictions, and the prioritization of uncharacterized proteins for experimental testing distinguish COMBREX from other publicly available microbial genomics resources. This article describes updates to COMBREX-DB since an initial description in the 2011 NAR Database Issue.

Resveratrol (RSV) has been reported to influence many biological processes, including the stimulation of cellular senescence and inhibition of epithelial-mesenchymal transition (EMT). In this research, we explored the mechanisms of RSV on EMT and cellular senescence through the expression of a DNA damage response (DDR) protein, Rad9, in breast and lung cancer cell lines. Upon treating breast and lung cancer cell lines with RSV at the concentrations of 10–50 μM, Rad9 expression was increased at both transcriptional and translational levels. The results indicated that RSV-induced Rad9 expression, mediated by DNA damage and ROS, can significantly suppress proliferation by activating cellular senescence, and diminishing the expression of EMT markers with concomitant downregulation of Slug in breast and lung cancer cell lines. By using a siRNA approach, RSV was shown to mediate cellular senescence and EMT through a Rad9-dependent mechanism. The treatment with RSV can inhibit the proliferation, EMT, and increase cellular senescence of breast and lung cancer cell lines by activating Rad9. Our results suggest that the breast and lung tumor suppressive activities of RSV are, at least in part, mediated by the upregulation of Rad9.

A shift of the delicate balance between apoptosis and survival-inducing signals determines the fate of neurons during the development of the central nervous system and its homeostasis throughout adulthood. Both pathways, promoting or protecting from apoptosis, trigger a transcriptional program. We conducted whole-genome expression profiling to decipher the transcriptional regulatory elements controlling the apoptotic/survival switch in cerebellar granule neurons following the induction of apoptosis by serum and potassium deprivation or their rescue by either insulin-like growth factor-1 (Igf1) or pituitary adenylyl cyclase-activating polypeptide (Pacap). Although depending on different upstream signaling pathways, the survival effects of Igf1 and Pacap converged into common transcriptional cascades, thus suggesting the existence of a general transcriptional program underlying neuronal survival.