Contraceptive and Infertility Target DataBase: a contraceptive drug development tool for targeting and analysis of human reproductive specific tissues†.

The long and challenging drug development process begins with discovery biology for the selection of an appropriate target for a specific indication. Target is a broad term that can be applied to a range of biological entities such as proteins, genes, and ribonucleic acids (RNAs). Although there are numerous databases available for mining biological entities, publicly available searchable, downloadable databases to aid in target selection for a specific disease or indication (e.

Soft Set Theory for Decision Making in Computational Biology under Incomplete Information.

The study of biological systems is complex and of great importance. There exist numerous approaches to signal transduction processes, including symbolic modeling of cellular adaptation. The use of formal methods for computational systems biology eases the analysis of cellular models and the establishment of the causes and consequences of certain cellular situations associated to diseases.

Epidermal Growth Factor Signaling towards Proliferation: Modeling and Logic Inference Using Forward and Backward Search.

In biological systems, pathways define complex interaction networks where multiple molecular elements are involved in a series of controlled reactions producing responses to specific biomolecular signals. These biosystems are dynamic and there is a need for mathematical and computational methods able to analyze the symbolic elements and the interactions between them and produce adequate readouts of such systems. In this work, we use rewriting logic to analyze the cellular signaling of epidermal growth factor (EGF) and its cell surface receptor (EGFR) in order to induce cellular proliferation.

Integrated analysis of breast cancer cell lines reveals unique signaling pathways.

Background: Cancer is a heterogeneous disease resulting from the accumulation of genetic defects that negatively impact control of cell division, motility, adhesion and apoptosis. Deregulation in signaling along the EgfR-MAPK pathway is common in breast cancer, though the manner in which deregulation occurs varies between both individuals and cancer subtypes.

Results: We were interested in identifying subnetworks within the EgfR-MAPK pathway that are similarly deregulated across subsets of breast cancers.

5'-AMP-activated protein kinase (AMPK) is induced by low-oxygen and glucose deprivation conditions found in solid-tumor microenvironments.

Low oxygen gradients (hypoxia and anoxia) are important determinants of pathological conditions under which the tissue blood supply is deficient or defective, such as in solid tumors. We have been investigating the relationship between the activation of hypoxia-inducible factor 1 (HIF-1), the primary transcriptional regulator of the mammalian response to hypoxia, and 5'-AMP-activated protein kinase (AMPK), another regulatory system important for controlling cellular energy metabolism. In the present study, we used mouse embryo fibroblasts nullizygous for HIF-1alpha or AMPK expression to show that AMPK is rapidly activated in vitro by both physiological and pathophysiological low-oxygen conditions, independently of HIF-1 activity.

Glucose utilization is essential for hypoxia-inducible factor 1 alpha-dependent phosphorylation of c-Jun.

Hypoxia and anoxia are important microenvironmental stresses that contribute to pathological events such as solid-tumor development. We have been investigating the effects of hypoxia and anoxia on expression of the proto-oncogene c-jun and the regulation of c-Jun/AP-1 transcription factors. In earlier work using genetically manipulated mouse embryo fibroblasts (mEFs), we found a functional relationship among c-jun expression, c-Jun N-terminal phosphorylation, and the presence of hypoxia-inducible factor 1 alpha (HIF-1 alpha), the oxygen-regulated subunit of the HIF-1 transcription factor.

Pathway logic: symbolic analysis of biological signaling.

The genomic sequencing of hundreds of organisms including homo sapiens, and the exponential growth in gene expression and proteomic data for many species has revolutionized research in biology. However, the computational analysis of these burgeoning datasets has been hampered by the sparse successes in combinations of data sources, representations, and algorithms. Here we propose the application of symbolic toolsets from the formal methods community to problems of biological interest, particularly signaling pathways, and more specifically mammalian mitogenic and stress responsive pathways.

The response of c-jun/AP-1 to chronic hypoxia is hypoxia-inducible factor 1 alpha dependent.

Hypoxia (low-oxygen tension) is an important physiological stress that influences responses to a wide range of pathologies, including stroke, infarction, and tumorigenesis. Prolonged or chronic hypoxia stimulates expression of the stress-inducible transcription factor gene c-jun and transient activation of protein kinase and phosphatase activities that regulate c-Jun/AP-1 activity. Here we describe evidence obtained by using wild-type and HIF-1 alpha nullizygous mouse embryonic fibroblasts (mEFs) that the induction of c-jun mRNA expression and c-Jun phosphorylation by prolonged hypoxia are completely dependent on the presence of the oxygen-regulated transcription factor hypoxia-inducible factor 1 alpha (HIF-1 alpha).