Vascular endothelial growth factor and its receptor (VEGF-VEGFR) system play a critical role in the regulation of angiogenesis and lymphangiogenesis in vertebrates. Each of the VEGF has specific receptors, which it activates by binding to the extracellular domain of the receptors, and, thus, regulates the angiogenic balance in the early embryonic and adult stages. However, de-regulation of the VEGF-VEGFR implicates directly in various diseases, particularly cancer. Moreover, tumor growth needs a dedicated blood supply to provide oxygen and other essential nutrients. Tumor metastasis requires blood vessels to carry tumors to distant sites, where they can implant and begin the growth of secondary tumors. Thus, investigation of signaling systems related to the human disease, such as VEGF-VEGFR, will facilitate the development of treatments for such illnesses.

We compared the incidence and severity of complications during and after closing- and opening-wedge high tibial osteotomy used for the treatment of varus arthritis of the knee, and identified the risk factors associated with the development of complications. In total, 104 patients underwent laterally based closing-wedge and 90 medial opening-wedge high tibial osteotomy between January 1993 and December 2006. The characteristics of each group were similar. All the patients were followed up for more than 12 months. We assessed the outcome using the Hospital for Special Surgery knee score, and recorded the complications. Age, gender, obesity (body mass index > 27.5 kg/m(2)), the type of osteotomy (closing versus opening) and the pre-operative mechanical axis were subjected to risk-factor analysis. The mean Hospital for Special Surgery score in the closing and opening groups improved from 73.4 (54 to 86) to 91.8 (81 to 100) and from 73.8 (56 to 88) to 93 (84 to 100), respectively. The incidence of complications overall and of major complications in both groups was not significantly different (p = 0.20 overall complication, p = 0.29 major complication). Logistic regression analysis adjusting for obesity and the pre-operative mechanical axis showed that obesity remained a significant independent risk factor (odds ratio = 3.23) of a major complication after high tibial osteotomy. Our results suggest that the opening-wedge high tibial osteotomy can be an alternative treatment option for young patients with medial compartment osteoarthritis and varus deformity.

The NADPH:2-ketopropyl-coenzyme M oxidoreductase/carboxylase (2-KPCC) is the terminal enzyme in a metabolic pathway that results in the conversion of propylene to the central metabolite acetoacetate in Xanthobacter autotrophicus Py2. This enzyme is an FAD-containing enzyme that is a member of the NADPH:disulfide oxidoreductase (DSOR) family of enzymes that include glutathione reductase, dihydrolipoamide dehydrogenase, trypanothione reductase, thioredoxin reductase, and mercuric reductase. In contrast to the prototypical reactions catalyzed by members of the DSOR family, the NADPH:2-ketopropyl-coenzyme M oxidoreductase/carboxylase catalyzes the reductive cleavage of the thioether linkage of 2-ketopropyl-coenzyme M, and the subsequent carboxylation of the ketopropyl cleavage product, yielding the products acetoacetate and free coenzyme M. The structure of 2-KPCC reveals a unique active site in comparison to those of other members of the DSOR family of enzymes and demonstrates how the enzyme architecture has been adapted for the more sophisticated biochemical reaction. In addition, comparison of the structures in the native state and in the presence of bound substrate indicates the binding of the substrate 2-ketopropyl-coenzyme M induces a conformational change resulting in the collapse of the substrate access channel. The encapsulation of the substrate in this manner is reminiscent of the conformational changes observed in the well-characterized CO2-fixing enzyme ribulose 1,5-bisphosphate carboxylase/oxidase (Rubisco).

Proliferating cell nuclear antigen (PCNA) is a critical eukaryotic replication accessory factor that supports DNA binding in DNA processing, such as DNA replication, repair, and recombination. PCNA consists of three toroidal-shaped monomers that encircle doublestranded DNA. The diverse functions of PCNA may be regulated by its interactions with partner proteins. Many of the PCNA partner proteins generally have a conserved PCNAinteracting peptide (PIP) motif, located at the N- or C- terminal region. The PIP motif forms a 310 helix that enters into the hydrophobic groove produced by an interdomain-connecting loop, a central loop, and a C-terminal tail in the PCNA. Post-translational modification of PCNA also plays a critical role in regulation of its function and binding partner proteins. Structural and biochemical studies of PCNA-protein will be useful in designing therapeutic agents, as well as estimating the outcome of anticancer drug development. This review summarizes the characterization of eukaryotic PCNA in relation to the protein structures, functions, and modifications, and interaction with proteins.