We review a diversity of mechanisms discovered in recent years that couple the different stages of gene expression. We then selleck kinase inhibitor speculate on the functional and evolutionary significance of this coupling and suggest certain systems-level

functionalities that might be optimized via the various coupling modes. In particular, we hypothesize that coupling is often an economic strategy that allows biological systems to respond robustly and precisely to genetic and environmental perturbations.”
“The human kallikrein-related peptidases (KLKs) comprise 15 members (KLK1-15) and are the single largest family of serine proteases. The KLKs are utilized, or proposed, as clinically important biomarkers and therapeutic targets of interest in cancer and neurodegenerative disease. All KLKs appear to be secreted as inactive pro-forms (pro-KLKs) that are activated extracellularly by specific proteolytic release of their N-terminal pro-peptide. This processing is a key step in the regulation of KLK function. Much recent work has been devoted to elucidating the potential for activation cascades

between members of the KLK family, with physiologically relevant KLK regulatory cascades now described in skin desquamation and semen liquefaction. Despite this expanding LXH254 chemical structure knowledge of KLK regulation, details regarding the potential for functional intersection of KLKs with other regulatory proteases are

essentially unknown. To elucidate such interaction potential, we have characterized the ability of proteases associated with thrombostasis to hydrolyze the pro-peptide sequences of the KLK family using a previously described pro-KLK fusion protein system. A subset of positive hydrolysis results were subsequently quantified with proteolytic assays using intact recombinant pro-KLK proteins. Pro-KLK6 and 14 can be activated by both plasmin and uPA, with plasmin being the best activator of pro-KLK6 identified to date. Pro-KLK11 and 12 can be activated by a broad-spectrum of thrombostasis proteases, with thrombin exhibiting a high degree of selectivity Aurora Kinase for pro-KLK12. The results show that proteases of the thrombostasis family can efficiently activate specific pro-KLKs, demonstrating the potential for important regulatory interactions between these two major protease families.”
“BACKGROUND AND IMPORTANCE: Cerebral revascularization continues to be an important technique for the treatment of cerebrovascular and vaso-occlusive diseases, and determination of appropriate graft sources and recipients is paramount to the success of the procedure. A tension-free anastomosis requires that harvested grafts be of an appropriate length to avoid complications.