UCP3 and its putative function: consistencies and controversies.

The physiological function of uncoupling protein 3 (UCP3) is as yet unknown. Based on its 57% homology to UCP1 whose physiologic function is uncoupling and thermogenesis, UCP3 was attributed with the function of mitochondrial uncoupling through proton-leak reactions. UCP3 is expressed selectively in muscle, a tissue in which it has been estimated that proton leak accounts for approx. 50% of resting energy metabolism. Genetic linkage, association and variant studies suggest a role for UCP3 in obesity and/or diabetes. Studies of the heterologous expression of UCP3 in yeast provide support for the idea that UCP3 can uncouple mitochondrial oxidative phosphorylation, but the physiological relevance of these results is questionable. In vitro studies of mitochondria from Ucp3(-/-) mice provide support, but there are no changes in resting metabolic rate (RMR) of mice. In vivo studies demonstrate increased ATP synthesis, but estimates of substrate oxidation rate indicate no change. Mice that greatly overexpress Ucp3 in muscle have increased RMR. Inconsistent with the function of uncoupling are the observations that fasting results in increased expression of UCP3, but no change in muscle proton leak. Moreover, fasting decreases energy expenditure in muscle. Expression patterns for Ucp3 and lipid-metabolism genes support a physiological role in fatty acid oxidation. Overall, findings support a role for Ucp3 in fatty acid metabolism that may have implications for obesity and/or Type II diabetes.

Functional genomics of plant photosynthesis in the fast lane using Chlamydomonas reinhardtii.

Oxygenic photosynthesis by algae and plants supports much of life on Earth. Several model organisms are used to study this vital process, but the unicellular green alga Chlamydomonas reinhardtii offers significant advantages for the genetic dissection of photosynthesis. Recent experiments with Chlamydomonas have substantially advanced our understanding of several aspects of photosynthesis, including chloroplast biogenesis, structure-function relationships in photosynthetic complexes, and environmental regulation. Chlamydomonas is therefore the organism of choice for elucidating detailed functions of the hundreds of genes involved in plant photosynthesis.

Crutch length: effect on energy cost and activity intensity in non-weight-bearing ambulation.

OBJECTIVE: To investigate the effect of forearm crutch length on energy cost in three-point, non-weight-bearing (NWB) ambulation. DESIGN: Double-blind repeated measures design using crutch length as the independent variable. SETTING: Overland walking circuit at a university campus. PARTICIPANTS: Volunteer, convenience sample of 20 subjects consisting of university students and staff without cardiovascular, respiratory, or orthopedic conditions. INTERVENTION: Subjects used a three-point, NWB gait with forearm crutches set to length using conventional guidelines, and at 2.5 cm above and below this value. MAIN OUTCOME MEASURES: Oxygen consumption, carbon dioxide production, heart rate, speed of ambulation, and perceived exertion under steady-state conditions. RESULTS: In terms of oxygen cost, ambulation with crutches set to the length recommended in conventional guidelines was not significantly more energy efficient than ambulation with either the longer or shorter crutches. Using crutches set 2.5 cm longer than conventional guidelines produced the lowest respiratory exchange ratio (Vco2/Vo2) and the lowest ratings of perceived exertion. However, none of these differences reached statistical significance. CONCLUSION: Since exact crutch length was not critical in terms of oxygen cost, walking speed, or perceived exertion during NWB ambulation, the importance of rigidly adhering to specific guidelines for setting crutch length was not substantiated in this study. Clinically, consideration of patient preference regarding crutch length (within 2.5 cm) can be advocated.

Abnormal fibrin structure and inhibition of fibrinolysis in patients with multiple myeloma.

Abnormal clot structures have been reported in patients with multiple myeloma, and purified immunoglobulin G (IgG) has been shown to influence fibrin assembly in purified systems. Recently fibrin structure has been demonstrated to be a major determinant of fibrinolytic rates. This study examined the effects of purified polyclonal and monoclonal myeloma IgG on fibrin structure and fibrinolysis in plasma clots. Clotting was initiated by the addition of thrombin (1.0 NIH units/ml) and calcium (10 mmol/L). Gelation was monitored as a time-dependent increase in optical density (633 nm). Fibrin fiber size (mu = mass-length ratio) was measured by scanning the gel from 800 to 400 nm. Two preparations of polyclonal IgG and plasma samples from 10 patients with myeloma were studied. Both Sandoglobulin (Sandoz Pharmaceuticals Corp.) and Gamimmune (Miles Inc., Cutter Biological) decreased final gel turbidity as the IgG concentration increased from 0 to 15 mg/ml. Because of its high maltose content, Gamimmune produced more-pronounced effects. Over a concentration range of 0 to 15 mg IgG per milliliter, mu decreased from 1.25 to 0.59 x 10(13) daltons/cm for Sandoglobulin and from 1.30 to 0.18 x 10(13) daltons/cm for Gamimmune. Polyclonal IgG at 15 mg/ml prolonged clot lysis induced by tissue-type plasminogen activator (tPA) from 800 seconds to > 12 hours. Similar effects were noted in myeloma clots. mu values in myeloma clots were significantly smaller than mu values in comparable normal clots. mu became smaller and lysis times became increasingly prolonged as the IgG level increased. High IgG concentrations induce thin fiber formation and impair fibrinolysis in plasma gels. These results demonstrate that fibrinolysis is inhibited in myeloma clots and that the degree of inhibition is correlated with IgG-mediated alterations in fibrin structure. Thin fibrin fibers may contribute to thrombotic risk in myeloma.

Quantitative assessment of platelet function and clot structure in patients with severe coronary artery disease.

The prothrombotic state of patients with coronary artery disease (CAD) can be attributed partially to platelet activity. Management of such patients is hindered by a lack of techniques to assess hemostatic function. This study used a sensitive technique to monitor platelet function by measuring platelet force development during clot retraction. This technique allowed simultaneous measurement of clot elastic modulus on the same sample. Fibrin mass-length ratio (mu), fibrinopeptide A, D-Dimer, von Willebrand's factor, thromboxane A2, platelet aggregation studies, and bleeding times also were performed. Fourteen patients with CAD were compared with 10 healthy volunteers. Despite more than 95% suppression of thromboxane B2 and prolongation bleeding times in patients taking aspirin, force development remained significantly elevated over healthy control patients (8,279 +/- 476 dynes versus 4,857 +/- 380 dynes, p < 0.0006). Patients not taking aspirin had normal bleeding times and force development of 19,110 +/- 3,700 dynes. Clot elastic moduli were enhanced in patients with CAD whether taking or not taking aspirin. Adenosine diphosphate and ristocetin-induced platelet aggregation were insensitive to the effect of aspirin in patients with CAD. Fibrinopeptide A, von Willebrand's factor, and D-Dimer levels were significantly elevated, and fibrin mass-length ratios were significantly larger in patients with CAD. Therefore, despite aspirin therapy, patients with severe CAD have evidence of persistent platelet activation and rigid clot structure. Monitoring of platelet force development may prove useful in delineating enhanced platelet function.