The global field of multi-family offices: An institutionalist perspective

We apply the notion of the organisational field to internationally operating multi-family offices. These organisations specialise on the preservation of enterprising and geographically dispersed families’ fortunes. They provide their services across generations and countries. Based on secondary data of Bloomberg’s Top 50 Family Offices, we show that they constitute a global organisational field that comprises two clusters of homogeneity. Clients may decide between two different configurations of activities, depending on their preferences regarding asset management, resource management, family management, and service architecture. The findings also reveal that multi-family offices make relatively similar value propositions all over the world. The distinctiveness of the clusters within the field is not driven by the embeddedness of the multi-family offices in different national environments or their various degrees of international experience. Rather, it is weakly affected by two out of four possible value propositions, namely the exclusiveness and the transparency of services

Reversing Blood Flows Act through klf2a to Ensure Normal Valvulogenesis in the Developing Heart

Heart valve anomalies are some of the most common congenital heart defects, yet neither the genetic nor the epigenetic forces guiding heart valve development are well understood. When functioning normally, mature heart valves prevent intracardiac retrograde blood flow; before valves develop, there is considerable regurgitation, resulting in reversing (or oscillatory) flows between the atrium and ventricle. As reversing flows are particularly strong stimuli to endothelial cells in culture, an attractive hypothesis is that heart valves form as a developmental response to retrograde blood flows through the maturing heart. Here, we exploit the relationship between oscillatory flow and heart rate to manipulate the amount of retrograde flow in the atrioventricular (AV) canal before and during valvulogenesis, and find that this leads to arrested valve growth. Using this manipulation, we determined that klf2a is normally expressed in the valve precursors in response to reversing flows, and is dramatically reduced by treatments that decrease such flows. Experimentally knocking down the expression of this shear-responsive gene with morpholine antisense oligonucleotides (MOs) results in dysfunctional valves. Thus, klf2a expression appears to be necessary for normal valve formation. This, together with its dependence on intracardiac hemodynamic forces, makes klf2a expression an early and reliable indicator of proper valve development. Together, these results demonstrate a critical role for reversing flows during valvulogenesis and show how relatively subtle perturbations of normal hemodynamic patterns can lead to both major alterations in gene expression and severe valve dysgenesis

Up-regulation of endothelin type B receptors in the human internal mammary artery in culture is dependent on protein kinase C and mitogen-activated kinase signaling pathways

<p>Abstract</p> <p>Background</p> <p>Up-regulation of vascular endothelin type B (ET_B) receptors is implicated in the pathogenesis of cardiovascular disease. Culture of intact arteries has been shown to induce similar receptor alterations and has therefore been suggested as a suitable method for, <it>ex vivo</it>, in detail delineation of the regulation of endothelin receptors. We hypothesize that mitogen-activated kinases (MAPK) and protein kinase C (PKC) are involved in the regulation of endothelin ET_Breceptors in human internal mammary arteries.</p> <p>Methods</p> <p>Human internal mammary arteries were obtained during coronary artery bypass graft surgery and were studied before and after 24 hours of organ culture, using <it>in vitro </it>pharmacology, real time PCR and Western blot techniques. Sarafotoxin 6c and endothelin-1 were used to examine the endothelin ET_Aand ET_Breceptor effects, respectively. The involvement of PKC and MAPK in the endothelin receptor regulation was examined by culture in the presence of antagonists.</p> <p>Results</p> <p>The endohtelin-1-induced contraction (after endothelin ET_Breceptor desensitization) and the endothelin ET_Areceptor mRNA expression levels were not altered by culture. The sarafotoxin 6c contraction, endothelin ET_Breceptor protein and mRNA expression levels were increased after organ culture. This increase was antagonized by; (1) PKC inhibitors (10 μM bisindolylmaleimide I and 10 μM Ro-32-0432), and (2) inhibitors of the p38, extracellular signal related kinases 1 and 2 (ERK1/2) and C-jun terminal kinase (JNK) MAPK pathways (10 μM SB203580, 10 μM PD98059 and 10 μM SP600125, respectively).</p> <p>Conclusion</p> <p>In conclusion, PKC and MAPK seem to be involved in the up-regulation of endothelin ET_Breceptor expression in human internal mammary arteries. Inhibiting these intracellular signal transduction pathways may provide a future therapeutic target for hindering the development of vascular endothelin ET_Breceptor changes in cardiovascular disease.</p

Hypoxia-inducible Factor-1 Activation in Nonhypoxic Conditions: The Essential Role of Mitochondrial-derived Reactive Oxygen Species

Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor for responses to low oxygen. Here we report that the generation of mitochondrial reactive oxygen species are essential for regulating HIF-1 in normal oxygen conditions in the vasculature

Piper sarmentosum inhibits ICAM-1 and Nox4 gene expression in oxidative stress-induced human umbilical vein endothelial cells

<p>Abstract</p> <p>Background</p> <p>Aqueous extract of <it>Piper sarmentosum </it>(AEPS) is known to possess antioxidant and anti-atherosclerotic activities but the mechanism responsible for it remains unclear. In early part of atherosclerosis, nuclear factor-kappa B (NF-κB) induces the expression of cellular adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1) and E-selectin. NADPH oxidase 4 (Nox4) is the predominant source of superoxide in the endothelial cells whereas superoxide dismutase 1 (SOD1), catalase (CAT) and glutathione peroxidase (GPx) are the antioxidant enzymes responsible for inactivating reactive oxygen species. The present study aimed to investigate the effects of AEPS on the gene expression of NF-κB, VCAM-1, ICAM-1, E-selectin, Nox4, SOD1, CAT and GPx in cultured human umbilical vein endothelial cells (HUVECs).</p> <p>Methods</p> <p>HUVECs were divided into four groups:- control; treatment with 180 μM hydrogen peroxide (H₂O₂); treatment with 150 μg/mL AEPS and concomitant treatment with AEPS and H₂O₂for 24 hours. Total RNA was extracted from all the groups of HUVEC using TRI reagent. Subsequently, qPCR was carried out to determine the mRNA expression of NF-κB, VCAM-1, ICAM-1, E-selectin, Nox4, SOD1, CAT and GPx. The specificity of the reactions was verified using melting curve analysis and agarose gel electrophoresis.</p> <p>Results</p> <p>When stimulated with H₂O₂, HUVECs expressed higher level of ICAM-1 (1.3-fold) and Nox4 (1.2-fold) mRNA expression. However, AEPS treatment led to a reduction in the mRNA expression of ICAM-1 (p < 0.01) and Nox4 (p < 0.05) in the H₂O₂-induced HUVECs. AEPS also upregulated the mRNA expression of SOD1 (p < 0.05), CAT (p < 0.01) and GPx (p < 0.05) in oxidative stress-induced HUVECs. There was no significant change in the mRNA expression of VCAM-1 and E-selectin.</p> <p>Conclusion</p> <p>The expressional suppression of ICAM-1 and Nox4 and induction of antioxidant enzymes might be an important component of the vascular protective effect of AEPS.</p

Drivers and technology-related obstacles in moving to multichannel retailing

Today, multichannel retailing is a key strategic issue for most retailers. Yet, while there are many drivers associated with retailers going multichannel so too are there technology-related obstacles, however, few prior empirical studies explore these themes. In light of this, by using a multi-case approach to understand the key drivers and technology-related obstacles associated with retailers moving to multichannel retailing our study makes two key contributions. First, we extend prior theory by providing novel empirical insights into the main drivers underpinning retailers using a multichannel strategy. We find that meeting customer needs and increasing sales were the primary drivers behind retailers using the strategy, although there is diversity in the way retailers respond to these motives. Second, we provide empirical support for a proposed theoretical framework which summarises the key technology-related obstacles retailers encounter when going multichannel, by stage of implementation. The framework reveals that retailers face technology-related obstacles when implementing a multichannel strategy due to the need to switch/acquire resources and achieve channel integration. Furthermore, the framework highlights that these resource and channel integration issues are often interrelated with each other and with other staff engagement and cultural issues, vary by retailer and stage of implementation, and pose greater obstacles to retailers using new and multiple channels than the extant literature suggests

Androgen Excess Produces Systemic Oxidative Stress and Predisposes to β-Cell Failure in Female Mice

In women, excess production of the male hormone, testosterone (T), is accompanied by insulin resistance. However, hyperandrogenemia is also associated with β-cell dysfunction and type 2 diabetes raising the possibility that androgen receptor (AR) activation predisposes to β-cell failure. Here, we tested the hypothesis that excess AR activation produces systemic oxidative stress thereby contributing to β-cell failure. We used normal female mice (CF) and mice with androgen resistance by testicular feminization (Tfm). These mice were exposed to androgen excess and a β-cell stress induced by streptozotocin (STZ). We find that following exposure to T, or the selective AR-agonist dehydrotestosterone (DHT), CF mice challenged with STZ, which are normally protected, are prone to β-cell failure and insulin-deficient diabetes. Conversely, T-induced predisposition to β-cell failure is abolished in Tfm mice. We do not observe any proapoptotic effect of DHT alone or in the presence of H2O2 in cultured mouse and human islets. However, we observe that exposure of CF mice to T or DHT provokes systemic oxidative stress, which is eliminated in Tfm mice. This work has significance for hyperandrogenic women; excess activation of AR by testosterone may provoke systemic oxidative stress. In the presence of a prior β-cell stress, this may predispose to β-cell failure

eNOS Protects from Atherosclerosis Despite Relevant Superoxide Production by the Enzyme in apoE−/− Mice

All three nitric oxide synthase (NOS) isoforms are expressed in atherosclerotic plaques. NOS enzymes in general catalyse NO production. However, under conditions of substrate and cofactor deficiency, the enzyme directly catalyse superoxide formation. Considering this alternative chemistry, the effects of NOS on key events in spontaneous hyperlipidemia driven atherosclerosis have not been investigated yet. Here, we evaluate how endothelial nitric oxide synthase (eNOS) modulates leukocyte/endothelial- (L/E) and platelet/endothelial- (P/E) interactions in atherosclerosis and the production of nitric oxide (NO) and superoxide by the enzyme. Intravital microscopy (IVM) of carotid arteries revealed significantly increased L/E-interactions in apolipoproteinE/eNOS double knockout mice (apoE(-/-)/eNOS(-/-)), while P/E-interactions did not differ, compared to apoE(-/-). eNOS deficiency increased macrophage infiltration in carotid arteries and vascular cell adhesion molecule-1 (VCAM-1) expression, both in endothelial and smooth muscle cells. Despite the expression of other NOS isoforms (inducible NOS, iNOS and neuronal NOS, nNOS) in plaques, Electron Spin Resonance (ESR) measurements of NO showed significant contribution of eNOS to total circulating and vascular wall NO production. Pharmacological inhibition and genetic deletion of eNOS reduced vascular superoxide production, indicating uncoupling of the enzyme in apoE(-/-) vessels. Overt plaque formation, increased vascular inflammation and L/E- interactions are associated with significant reduction of superoxide production in apoE(-/-)/eNOS(-/-) vessels. Therefore, lack of eNOS does not cause an automatic increase in oxidative stress. Uncoupling of eNOS occurs in apoE(-/-) atherosclerosis but does not negate the enzyme's strong protective effects