Abstract-Recent studies have indicated the importance of cholesterol-rich membrane lipid rafts (LRs) in oxidative stress-induced signal transduction. Reduced nicotinamide-adenine dinucleotide phosphate (NADPH) oxidases, the major sources of reactive oxygen species, are implicated in cardiovascular diseases, including hypertension. We tested the hypothesis that NADPH oxidase subunits and activity are regulated by LRs in human renal proximal tubule cells. We report that a high proportion of p22 phox and the small GTPase Rac1 are expressed in LRs in human renal proximal tubule cells.

Abstract-NADPH oxidase (Nox)-dependent reactive oxygen species production is implicated in the pathogenesis of cardiovascular diseases, including hypertension. We tested the hypothesis that oxidase subunits are differentially regulated in renal proximal tubules from normotensive and spontaneously hypertensive rats. Basal Nox2 and Nox4, but not Rac1, in immortalized renal proximal tubule cells and brush border membranes were greater in hypertensive than in normotensive rats. However, more Rac1 was expressed in lipid rafts in cells from hypertensive rats than in cells from normotensive rats; the converse was observed with Nox4, whereas Nox2 expression was similar. The D 1 -like receptor agonist fenoldopam decreased Nox2 and Rac1 protein in lipid rafts to a greater extent in hypertensive than in normotensive rats. Basal oxidase activity was 3-fold higher in hypertensive than in normotensive rats but was inhibited to a greater extent by fenoldopam in normotensive (58Ϯ3.3%) than in hypertensive rats (31Ϯ5.2%; PϽ0.05; nϭ6 per group). Fenoldopam decreased the amount of Nox2 that coimmunoprecipitated with p67 phox in cells from normotensive rats. D 1 -like receptors may decrease oxidase activity by disrupting the distribution and assembly of oxidase subunits in cell membrane microdomains. The cholesterol-depleting reagent methyl-␤-cyclodextrin decreased oxidase activity and cholesterol content to a greater extent in hypertensive than in normotensive rats. The greater basal levels of Nox2 and Nox4 in cell membranes and Nox2 and Rac1 in lipid rafts in hypertensive rats than in normotensive rats may explain the increased basal oxidase activity in hypertensive rats. Key Words: NADPH oxidase Ⅲ dopamine receptor Ⅲ reactive oxygen species Ⅲ lipid rafts T he NADPH oxidase (Nox) enzyme family is a major source of reactive oxygen species (ROS), eg, superoxide anion, hydrogen peroxide, and the hydroxyl radical. 1,2 Noxdependent ROS regulate diverse cellular processes, including angiotensin II-mediated renal growth and cardiovascular remodeling. [3][4][5][6] The increased generation of ROS by Nox contributes to human 5-7 and animal hypertension. 8 -15 Nox activity and superoxide formation are increased in vascular smooth muscle, 5,13 endothelial, 4,14 and neural cells 15 in genetic and acquired hypertension. The renal contribution to the pathogenesis of hypertension has also been ascribed to increased ROS production. [7][8][9][10]12,14 Lipid rafts (LRs) are membrane microdomains composed of glycosylphosphatidylinositol-linked proteins, glycosphingolipids, and cholesterol. 16 -19 Caveolae and LRs have been implicated in protein trafficking and signal transduction. 16 -19 They also serve as compartments for the recruitment of cell signaling components and enzymes to increase the efficient and rapid coupling of receptors to Ͼ1 effector system. G protein-coupled receptors, including dopamine receptors, are associated with caveolar and noncaveolar LRs. 16 -20 We and others have reported the presence of noncaveolar LRs in immortal...

Purpose This paper aims to investigate the complexity of collaborations in supply chain networks, particularly the influence of horizontal collaborations (e.g. international joint ventures) on vertical collaborations (e.g. supplier–manufacturer partnering relationships). Design/methodology/approach A multiple case study including four horizontal collaborations and five vertical collaborations within a supply chain network is presented in the context of the Chinese automotive industry. Data interpretation from interviews is structured by key collaborative activities and collaborative behaviors. Findings The analysis highlights a variety of collaborative behaviors under different types of collaboration and their interaction. The complexity of collaboration is revealed in a range of dimensions including culture diversity, drivers/facilitators, competitive/collaborative advantages and the engagement of all. Collaboration evolves as the structure of the supply chain changes; the key is to appreciate the existence of cooperation, competition and culture conflicts and to manage the trade-offs. Research limitations/implications A window of opportunity is presented for future research to investigate the complexity of supply chain collaboration in a wider industrial or geographical context, including statistical validation and comparative analysis. Practical implications A contingent view on supply chain collaboration is promoted to practitioners (e.g. international supply chain managers), where collaborative activities should be aligned with the motive and type of business relationships which may change as collaboration develops. Originality/value A rare empirical study captures the complexity of supply chain collaboration including the interaction between different forms. A dynamic collaboration approach recognizes the changing process, varying cooperation behaviors as well as characteristics of partners which have not been sufficiently reflected in the literature.

NADPH oxidases are the major sources of reactive oxygen species in cardiovascular, neural, and kidney cells. The NADPH oxidase 5 (NOX5) gene is present in humans but not rodents. Because Nox isoforms in renal proximal tubules (RPTs) are involved in the pathogenesis of hypertension, we tested the hypothesis that NOX5 is differentially expressed in RPT cells from normotensive (NT) and hypertensive subjects (HT). We found that NOX5 mRNA, total NOX5 protein, and apical membrane NOX5 protein were 4.2±0.7-fold, 5.2±0.7-fold, and 2.8±0.5-fold greater in HT than NT. Basal total NADPH oxidase activity was 4.5±0.2-fold and basal NOX5 activity in NOX5 immunoprecipitates was 6.2±0.2-fold greater in HT than NT (P=<0.001, n=6–14/group). Ionomycin increased total NOX and NOX5 activities in RPT cells from HT (P<0.01, n=4, ANOVA), effects that were abrogated by pre-treatment of the RPT cells with diphenylene-iodonium or superoxide dismutase. Silencing NOX5 using NOX5-siRNA decreased NADPH oxidase activity (−45.1±3.2% vs. mock-siRNA, n=6–8) in HT. D1-like receptor stimulation decreased NADPH oxidase activity to a greater extent in NT (−32.5±1.8%) than HT (−14.8±1.8). In contrast to the marked increase in expression and activity of NOX5 in HT, NOX1 mRNA and protein were minimally increased in HT, relative to NT; total NOX2 and NOX4 proteins were not different between HT and NT, while the increase in apical RPT cell membrane NOX1, NOX2, and NOX4 proteins in HT, relative to NT, was much less than those observed with NOX5. Thus, we demonstrate, for the first time, that NOX5 is expressed in human RPT cells and to greater extent than the other Nox isoforms in HT than NT. We suggest that the increased expression of NOX5, which may be responsible for the increased oxidative stress in RPT cells in human essential hypertension, is caused, in part, by a defective renal dopaminergic system.

The cardio-ankle vascular index (CAVI) has been widely accepted as a good indicator of arteriosclerosis. However, the lack of a reliable diagnostic criterion for CAVI hampers the proper clinical screening for arteriosclerosis using CAVI and impedes the prompt treatment of cardiovascular disease (CVD). There is an urgent need to determine a criterion for CAVI in arteriosclerosis prevention. We conducted a cross-sectional study to determine this criterion based on receiver operating characteristic (ROC) analyses in a Chinese population consisting of 328 participants. CAVI was measured in duplicate, and carotid ultrasound detection was performed in a quiet environment by well-trained physicians. After multivariate adjustment, CAVI was positively associated with the risk of carotid arteriosclerosis. Compared with participants in the lowest tertile of CAVI (5.15-7.40), those in the medium (7.41-8.65) and highest (8.66-13.60) tertiles had odds ratios (95% confidence interval) of 2.2 (1.0, 4.9) and 4.4 (1.5, 13.3), respectively, for developing carotid arteriosclerosis (P trend=0.007). The areas under the ROC curve (AUC) of the male, female and pooled populations were 0.789, 0.897 and 0.856, respectively. The cutoff point of CAVI≥8.0 resulted in the largest sensitivity and specificity. Furthermore, CAVI and age acted synergistically to increase the risk of carotid arteriosclerosis. CAVI≥8.0 may be an optimal cutoff point for carotid arteriosclerosis prediction. The older population with higher CAVI scores had a higher risk of carotid arteriosclerosis. Additional large prospective studies are needed to confirm our findings.

This study explores a performance measurement system for a dynamic supply chain partnership in a cross-cultural context. An initial framework is constructed by reviewing the existing literature, followed by an in-depth case study in the Chinese automotive industry, where the framework is refined to address the multi-cultural setting. A performance measurement, system which includes the relationship strategy and operational measurement criteria for a supply chain partnership, has been developed. The relationship strategy contains elements of strategy orientation, management style, interdependence, mutual organisational characteristics and common goals. The operational measurement criteria consist of commitment, trust, communication behaviour, information sharing, participation decision, quality, production performance, delivery, cost, supplier strength, attitude, compromise and loyalty. The last three operational measurement criteria are found to be particularly relevant to the cross-cultural feature. While existing studies tend to focus on either specific measures or individual organisations, this paper for the first time proposes a comprehensive framework to measure the performance of supply chain partnerships. The crosscultural perspective provides a further unique view on how a performance measurement system can be responsive to the dynamics in practice.Keywords: supply chain partnership; performance measures; case study; automotive industry; cross-cultural collaboration 1: Literature reviewSupply chain partnership (SCPR) management and performance measurement have been theorized as a crucial means for manufacturers to achieve sustainable competitive advantage and superior performance (Lee and Whang 2004;Hult, Ketchen and Arrfelt 2007; Cousins, Lawson and Squire 2008; Vanpoucke, Vereeckbe and Boyer 2014). Cao and Zhang (2011) noted that a good relationship with suppliers can give a manufacturer competitive advantage over others in the marketplace. Hence, much attention has been paid in the literature to developing effective SCPR, where the importance of partnership and performance to the entire supply chain is particularly stressed (Ellram 1991;Macbeth and Ferguson 1994;Landeros et al. 1995; New 1996;Maloni and Benton 1997).Performance can be defined as a metric used to quantify the efficiency and/or effectiveness of an action (Neely et al. 1995). Within the context of SCPR, performance of both manufacturers and suppliers should be taken into account, and an effective measurement system adopted to monitor their relationship (Chan and Qi 2003;Gunasekaran, Patel and Tirtiroglu 2001). On the one hand, supplier performance is vital to the success of the manufacturer-supplier relationship when measuring individual participants' input into the supply chain management process (Cousins et al. 2008). On the other hand, manufacturer performance is narrower, and assesses the prospective relationship and organisational capabilities in relation to company performance SCPR is a close, cooperative relationship, formed by tw...

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