Premature impairment of methylation pathway and cardiac metabolic dysfunction in fa/fa obese Zucker rats

Increasing evidence suggests that obesity is a chronic inflammatory disease, in which adipose tissue is involved in a network of endocrine signals to modulate energy homeostasis. These oxidative-inflammatory pathways, which are associated with cardiovascular complications, are also observed during the aging process. In this study, we investigated the interaction between aging and the development of obesity in a hyperphagic rat model. Metabolic profiles of the liver, white adipose tissue (WAT) and heart from young and adult Zucker lean (fa/+) and obese (fa/fa) rats were characterized using a (1)H NMR-based metabonomics approach. We observed premature metabolic modifications in all studied organs in obese animals, some of which were comparable to those observed in adult lean animals. In the cardiac tissue, young obese rats displayed lower lactate and scyllo-inositol levels associated with higher creatine, choline and phosphocholine levels, indicating an early modulation of energy and membrane metabolism. An early alteration of the hepatic methylation and transsulfuration pathways in both groups of obese rats indicated that these pathways were affected before diabetic onset. These findings therefore support the hypothesis that obesity parallels some metabolic perturbations observed in the aging process and provides new insights into the metabolic modifications occurring in pre-diabetic state.

Creating a world class business through a merger of two equals: an interview with Paul Walsh, Chief Executive Officer of Diageo Plc

Purpose – The purpose of this paper is to explore, from a practical point-of-view, a number of key strategic issues that critically influence organisations' competitiveness. Design/methodology/approach – The paper is based on a semi-structured interview with Mr Paul Walsh, CEO of Diageo. Diageo is a highly successful company and Mr Walsh has played a central role in making Diageo the number one branded drink company in the world. Findings – The paper discusses the key attributes of successful merger, lessons from a complex cross boarder acquisition, rationale for strategic alliance with competitors, distinctive resources, and the role of corporate social responsibility. Research limitations/implications – It is not too often that management scholars have the opportunity to discuss with the CEOs of large multinationals the rational of key strategic decisions. In this paper these issues are explored from the perspective of a CEO of a large and successful company. The lessons, while not generalisable, offer unique insights to students of management and management researchers. Originality/value – The paper offers a bridge between theory and practice. It demonstrates that from Diageo's perspective the distinctive capabilities are intangible. It also offers insight into how to successfully execute strategic decision. In terms of originality it offers a view from the top, which is often missing from strategy research.

BSkyB transformation from a new loss-making venture to a successful organisation: case study and interview with Jeremy Darroch, Chief Executive of British Sky Broadcasting Group Plc

Purpose – This paper aims to articulate strategic dilemmas faced by a Chief Executive of a highly successful company and how such dilemmas were resolved. Design/methodology/approach – The case is based on a semi-structured interview with Mr Jeremy Darroch – Chief Executive of BSkyB – and analysis of documentary evidence. Findings – It is often difficult to implement strategies that simultaneously yield high organic growth rate, innovation, and a healthy balance-sheet. The paper sheds light on how Sky has met this challenge. Research limitations/implications – The research offers a unique insight into the views of a principal strategist and articulates the background to offer context, however, because of its design the findings are not generalisable. Originality/value – Very few articles offer insight into the thinking of those with principal responsibility for design and delivery of strategy. This paper offers such an insight based on a detailed interview with a highly successful Chief Executive.

Building from scratch a marketing services giant by acquisition: case study and interview with Sir Martin Sorrell, Chief Executive of WPP

Purpose – Mergers and acquisitions are among the most intensely used strategic decisions. Yet research by both academics and consulting groups suggests that many mergers and acquisitions fail to add value. On the other hand there are many companies that successfully use mergers and acquisition to grow and add shareholder value. One such company is WPP. The aim of this paper is to explore why WPP has been successful in its acquisition strategy while so many other companies fail. Design/methodology/approach – The paper draws on documentary evidence and a semi-structured interview with Sir Martin Sorrell – Chief Executive and founder of WPP. Research limitations/implications – The case study offers a unique insight into thinking of a successful acquirer and sheds light on how mergers and acquisitions are managed by WPP. However, because of its design the findings are not generalisable. Originality/value – This case study sheds light on how mergers and acquisitions can be used to create a £9 billion company from a standing start. Furthermore, very few case studies offer insight into the thinking of entrepreneurial Chief Executives who established the business, grew it to become the largest and most profitable marketing services company in the world and engineered close to 300 acquisitions.

Successful strategy making in Bupa not-for-profit provident: a case study and interview with Mr Ray King, chief executive of Bupa

Purpose – The focus of extant strategy literature is on for-profit organisations and within these group public organisations. There are other forms of organisations and following the deep recession of 2008 there is greater interest in other forms of organisation. In this case study and interview the aim is to examine strategy, strategic decisions and strategic management of a not-for-profit provident. Design/methodology/approach – The paper draws on documentary evidence and a semi-structured interview with Ray King, chief executive of Bupa. The perspective of CEO is key in strategy and such perspectives are relatively rarer. Findings – Bupa invests its surplus to provide better healthcare. Free from the pressures of quarterly reporting and shareholders it can pursue long-term value creation for members rather than short-term surpluses. Research limitations/implications – The case study and interview offers a unique insight into strategy-making within a successful mutual provident that has grown organically and externally becoming an international leader in health insurance. Originality/value – This case study sheds light on strategy-making within a not-for-profit provident that has diversified and grown significantly over the past six decades. Furthermore, very few case studies offer insight into the thinking of a chief executive who has successfully managed a business in a turbulent environment.

Executive project management structure and the challenges acing its adoption in the Nigerian construction industry

Project management (PM) is a globally recognized discipline and has been widely adopted within the construction industry. Despite advancements in the PM discipline, the ineffective traditional management system, typical of the non-executive PM structure, is still widely used in the Nigerian construction industry. The aim of this paper is thus to explore the challenges facing the adoption of the executive PM structure in Nigeria. The paper first assesses the level of growth of PM in Nigeria using UK best practices as a benchmark and identifies the key PM characteristics in the two countries. Focus group interviews were used to collect the primary data for the study and content analysis was used to present the results in a thematic format. The study revealed the key barriers to the adoption of an executive PM structure in Nigeria as a lack of proper awareness, unfavorable policies, skill shortages, the traditional culture of stakeholders and the absence of a regulatory body. It is recommended that the government, as a major player/client in the Nigerian construction industry, should lead the campaign to change the traditional industry approach to project management. This is necessary if construction stakeholders in Nigeria are to be educated and encouraged towards adopting and putting into practice effective PM.

Plasma free fatty acids do not provide the link between obesity and insulin resistance or β-cell dysfunction: results of the Reading, Imperial, Surrey, Cambridge, Kings (RISCK) study

Aims To investigate the relationship between adiposity and plasma free fatty acid levels and the influence of total plasma free fatty acid level on insulin sensitivity and β-cell function. Methods An insulin sensitivity index, acute insulin response to glucose and a disposition index, derived from i.v. glucose tolerance minimal model analysis and total fasting plasma free fatty acid levels were available for 533 participants in the Reading, Imperial, Surrey, Cambridge, Kings study. Bivariate correlations were made between insulin sensitivity index, acute insulin response to glucose and disposition index and both adiposity measures (BMI, waist circumference and body fat mass) and total plasma free fatty acid levels. Multivariate linear regression analysis was performed, controlling for age, sex, ethnicity and adiposity. Results After adjustment, all adiposity measures were inversely associated with insulin sensitivity index (BMI: β = −0.357; waist circumference: β = −0.380; body fat mass: β = −0.375) and disposition index (BMI: β = −0.215; waist circumference: β = −0.248; body fat mass: β = −0.221) and positively associated with acute insulin response to glucose [BMI: β = 0.200; waist circumference: β = 0.195; body fat mass β = 0.209 (P values <0.001)]. Adiposity explained 13, 4 and 5% of the variation in insulin sensitivity index, acute insulin response to glucose and disposition index, respectively. After adjustment, no adiposity measure was associated with free fatty acid level, but total plasma free fatty acid level was inversely associated with insulin sensitivity index (β = −0.133), acute insulin response to glucose (β = −0.148) and disposition index [β = −0.218 (P values <0.01)]. Plasma free fatty acid concentration accounted for 1.5, 2 and 4% of the variation in insulin sensitivity index, acute insulin response to glucose and disposition index, respectively. Conclusions Plasma free fatty acid levels have a modest negative association with insulin sensitivity, β-cell secretion and disposition index but no association with adiposity measures. It is unlikely that plasma free fatty acids are the primary mediators of obesity-related insulin resistance or β-cell dysfunction.

Foreign executive appointments: a multilevel examination

As multinational enterprises (MNE) expand, their attachment to the country of origin is challenged by the need to adapt to an increasingly diverse geographical posture. We examine how these countervailing forces affect top management team (TMT) composition and test a model that associates foreign executive appointments with individual- and firm-level antecedents. Using multilevel data comprising 1,446 TMT appointments at 360 large European firms between 2001 and 2005, we show that individual experiential characteristics, the type of TMT function, prior performance of the MNE, and the MNE’s overall degree of internationalization are associated with foreign TMT appointments. We discuss how our findings contribute to the international business literature and complement recent research on the internationalization of TMTs.

Clonal expansion of early to mid-life mitochondrial DNA point mutations drives mitochondrial dysfunction during human ageing

Age-related decline in the integrity of mitochondria is an important contributor to the human ageing process. In a number of ageing stem cell populations, this decline in mitochondrial function is due to clonal expansion of individual mitochondrial DNA (mtDNA) point mutations within single cells. However the dynamics of this process and when these mtDNA mutations occur initially are poorly understood. Using human colorectal epithelium as an exemplar tissue with a well-defined stem cell population, we analysed samples from 207 healthy participants aged 17-78 years using a combination of techniques (Random Mutation Capture, Next Generation Sequencing and mitochondrial enzyme histochemistry), and show that: 1) non-pathogenic mtDNA mutations are present from early embryogenesis or may be transmitted through the germline, whereas pathogenic mtDNA mutations are detected in the somatic cells, providing evidence for purifying selection in humans, 2) pathogenic mtDNA mutations are present from early adulthood (<20 years of age), at both low levels and as clonal expansions, 3) low level mtDNA mutation frequency does not change significantly with age, suggesting that mtDNA mutation rate does not increase significantly with age, and 4) clonally expanded mtDNA mutations increase dramatically with age. These data confirm that clonal expansion of mtDNA mutations, some of which are generated very early in life, is the major driving force behind the mitochondrial dysfunction associated with ageing of the human colorectal epithelium.

Imbalanced functional link between executive control network and reward network explain the online-game seeking behaviors in Internet gaming disorder

Literatures have shown that Internet gaming disorder (IGD) subjects show impaired executive control and enhanced reward sensitivities than healthy controls. However, how these two networks jointly affect the valuation process and drive IGD subjects' online-game-seeking behaviors remains unknown. Thirty-five IGD and 36 healthy controls underwent a resting-states scan in the MRI scanner. Functional connectivity (FC) was examined within control and reward network seeds regions, respectively. Nucleus accumbens (NAcc) was selected as the node to find the interactions between these two networks. IGD subjects show decreased FC in the executive control network and increased FC in the reward network when comparing with the healthy controls. When examining the correlations between the NAcc and the executive control/reward networks, the link between the NAcc - executive control network is negatively related with the link between NAcc - reward network. The changes (decrease/increase) in IGD subjects' brain synchrony in control/reward networks suggest the inefficient/overly processing within neural circuitry underlying these processes. The inverse proportion between control network and reward network in IGD suggest that impairments in executive control lead to inefficient inhibition of enhanced cravings to excessive online game playing. This might shed light on the mechanistic understanding of IGD.