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Inner ear proteomics: a fad or hear to stay.

Proteomics, the large-scale analysis of the structure and function of proteins, as well as of protein-protein interactions, has evolved into a major component of 'systems analysis'. This requires the integration of information from different sources and at multiple levels, and involves two distinct parameters, (1) high-throughput protein separation, identification, and characterization, and (2) the extension of the obtained analytical data for the determination of the physiological function. The inner ear poses exceptional challenges to the study of proteomics because of its minute size, poor accessibility, association with complex fluid spaces, and diversity of cell types. Various approaches to the study of proteomics of the inner ear are presented, and success stories, noteworthy failures and what lies ahead, will be discussed.

Animals↗

Expression of the secreted FAD-dependent sulfydryl oxidase (QSOX) in the guinea pig central nervous system.

cpQSOx1 is a member of the QSOx family of proteins, expressed in the guinea pig (Cavia porcellus) and ortholog of the rat rQSOx1. In this study, in vitro experiments were conducted and showed that, as other member of this family, cpQSOx1 has a sulfydryl oxidase activity, and is a secreted protein. Then, the expression of this enzyme was researched in the guinea pig brain, as very little information exists yet on the expression of QSOx family members in the central nervous system. By immunohistochemistry, RT-PCR and in situ hybridization, cpQSOx1 is synthesized by neurons throughout the whole guinea pig central nervous system. Reticular structures as the basal forebrain, reticular thalamic nucleus and reticular nuclei of the brainstem contained the densest labeling. These results are discussed in terms of putative roles of this protein in synaptic strengthening and in redox activities.

Animals↗

In situ saphenous vein bypass grafts for limb salvage. A current fad or a viable alternative to reversed vein bypass grafts?

Revascularization of the lower extremity using the in situ saphenous vein bypass graft has resurfaced as a clinical alternative to reversal of the saphenous vein. Early patency rates have been excellent, however, concern has been raised about the durability of the in situ technique. Our total experience with this technique has been reviewed to evaluate its effectiveness on a teaching vascular service. Seventy-six limbs in 71 patients were revascularized using the in situ technique. The distal anastomosis was created at the below-the-knee popliteal level in 26 limbs and at the infrapopliteal level in 50 limbs. Operative assessment of the vein quality showed 42 percent to be phlebitic or less than 4 mm in diameter. Hospital mortality was 0 and late mortality was 8 percent. Cumulative life table analysis showed the graft patency rate to be 89 percent 1 month postoperatively, 82 percent at 1 year, 77 percent at 2 years, and 72 percent up to 4 year postoperatively. Patency was independent of runoff to the pedal arch and the level of the distal anastomosis. Limb salvage at 4 years was 83 percent for distal popliteal grafts and 79 percent for infrapopliteal reconstructions. Our results indicate that the long-term durability of the in situ saphenous vein graft is excellent despite suboptimal veins and poor runoff. When performed properly, it is the preferred technique for arterial reconstruction below the knee joint.

Adult↗

FAD-containing polyamine oxidases: a timely challenge for researchers in biochemistry and physiology of plants.

Recent investigations on plant polyamine oxidase (PAO) are reviewed. The enzyme belongs to a new class of flavoenzymes with similar structural features including, among others, monoamine oxidase. Plant PAOs catalyse the oxidation of the polyamine substrates spermidine and spermine. The reaction products are propane-1,3-diamine and 1-pyrroline or 1-(3-aminopropyl)pyrrolinium, respectively, along with hydrogen peroxide. Plant PAOs are predominantly localised in the cell wall. Purification procedures and molecular properties of several plant PAOs are compared. A special attention is being paid to the recently solved crystal structure of the maize enzyme and its implications for the substrate binding and catalytic mechanism. Substrate specificity and inhibitors of plant PAOs are also described. The potential roles for PAO-generated H(2)O(2) in lignin biosynthesis and cell wall cross-linking reactions, which may regulate growth and contribute to cell defence, are discussed.

Journal Article↗

A new paradigm for neurotoxicity by FAD mutants of betaAPP: a signaling abnormality.

We have demonstrated that normal betaAPP695 behave as a signaling receptor and indicated that point mutations at V642 create autoactive betaAPP in signal transduction. Cellular expression of those familial Alzheimer's disease-associated mutants causes neuronal cells to undergo apoptotic death; and procedures inhibiting the signal of normal betaAPP block the mutant-induced apoptosis. We have also shown that the mutant-induced death is mediated by intracellular G protein activity but not by secretion of Abeta peptides. Accordingly, the mutant-induced death requires a cytoplasmic domain but not the 41st and 42nd residues of the Abeta region. These studies provide a novel insight that betaAPP may play a normal role as a death receptor and that Alzheimer's disease-relevant abnormality occurred in this function may lead neurons to suicidal degeneration.

Alzheimer Disease↗