Regulation of the fibrosis and angiogenesis promoter SPARC/osteonectin in human adipose tissue by weight change, leptin, insulin, and glucose

This is the final version of the article. Available from the publisher via the DOI in this record.OBJECTIVE: Matricellular Secreted Protein, Acidic and Rich in Cysteine (SPARC), originally discovered in bone as osteonectin, is a mediator of collagen deposition and promotes fibrosis. Adipose tissue collagen has recently been found to be linked with metabolic dysregulation. Therefore, we tested the hypothesis that SPARC in human adipose tissue is influenced by glucose metabolism and adipokines. RESEARCH DESIGN AND METHODS: Serum and adipose tissue biopsies were obtained from morbidly obese nondiabetic subjects undergoing bariatric surgery and lean control subjects for analysis of metabolic markers, SPARC, and various cytokines (RT-PCR). Additionally, 24 obese subjects underwent a very-low-calorie diet of 1,883 kJ (450 kcal)/day for 16 weeks and serial subcutaneous-abdominal-adipose tissue (SCAT) biopsies (weight loss: 28 +/- 3.7 kg). Another six lean subjects underwent fast-food-based hyperalimentation for 4 weeks (weight gain: 7.2 +/- 1.6 kg). Finally, visceral adipose tissue explants were cultured with recombinant leptin, insulin, and glucose, and SPARC mRNA and protein expression determined by Western blot analyses. RESULTS: SPARC expression in human adipose tissue correlated with fat mass and was higher in SCAT. Weight loss induced by very-low-calorie diet lowered SPARC expression by 33% and increased by 30% in adipose tissue of subjects gaining weight after a fast-food diet. SPARC expression was correlated with leptin independent of fat mass and correlated with homeostasis model assessment-insulin resistance. In vitro experiments showed that leptin and insulin potently increased SPARC production dose dependently in visceral adipose tissue explants, while glucose decreased SPARC protein. CONCLUSIONS: Our data suggest that SPARC expression is predominant in subcutaneous fat and its expression and secretion in adipose tissue are influenced by fat mass, leptin, insulin, and glucose. The profibrotic effects of SPARC may contribute to metabolic dysregulation in obesity.This work was supported by Diabetes UK, Swedish Research Council (11285), University Hospital of Linkoping Research Funds; Diabetes Research Centre of Linkoping University; and the Gamla Tjaenarinnor Foundation. No potential conflicts of interest relevant to this article were reported. Parts of this study were presented in abstract form at the 69th Scientific Sessions of the American Diabetes Association, New Orleans, Louisiana, 5–9 June 2009

Research data supporting: Long-lived polarization memory in the electronic states of lead-halide perovskites from local structural dynamics

Experimental dat

Research data supporting: Long-lived polarization memory in the electronic states of lead-halide perovskites from local structural dynamics

Experimental dat

Alibaba: Jack Ma's unique growth strategy and the future of its global development in the Chinese digital business industry

China’s B2B businesses have gained immensely from the surge in social media users—with Alibaba, who have been at the forefront of the movement, benefitting the greatest. When compared to typical Western B2B companies, Alibaba has pursued a unique growth strategy—in line with the Chinese business ethos, through maintaining strong relations with the government as well as their gradual transition into the manufacturing sector. This research will therefore investigate Alibaba’s growth strategies through the lens of Chinese traditional norms to discern whether their development phases are exclusive to Alibaba, or whether it can be emulated by emerging e-commerce firms, also. Thus, Alibaba’s early business decisions will be compared to that of their Western digital business counterparts, analysing which factors shaped their successes, whether it be their development strategies or Ma’s own persona. Ultimately, Alibaba’s global status in the e-commerce industry going forward will be assessed to determine the relative likelihood of their future growth initiatives—addressing in the process whether their standing as the global leader of online business is temporary or whether it will fundamentally change the course of the industry

A functional variant in the CFI gene confers a high risk of age-related macular degeneration.

Item does not contain fulltextUp to half of the heritability of age-related macular degeneration (AMD) is explained by common variants. Here, we report the identification of a rare, highly penetrant missense mutation in CFI encoding a p.Gly119Arg substitution that confers high risk of AMD (P = 3.79 x 10(-6); odds ratio (OR) = 22.20, 95% confidence interval (CI) = 2.98-164.49). Plasma and sera from cases carrying the p.Gly119Arg substitution mediated the degradation of C3b, both in the fluid phase and on the cell surface, to a lesser extent than those from controls. Recombinant protein studies showed that the Gly119Arg mutant protein is both expressed and secreted at lower levels than wild-type protein. Consistent with these findings, human CFI mRNA encoding Arg119 had reduced activity compared to wild-type mRNA encoding Gly119 in regulating vessel thickness and branching in the zebrafish retina. Taken together, these findings demonstrate that rare, highly penetrant mutations contribute to the genetic burden of AMD

Diplomatic and corporate networks: Bridges to foreign locations

Firms and governments operate in broad networks in which the home government and its diplomatic service are a critical node – or a “referral point” – between firms and potential partners in foreign locations. Thus diplomatic relations between countries matter for the choice of foreign investment location. Using a network perspective, we argue that the extent to which good diplomatic relations induce firms to invest in friendly host countries depends on their political connections to home governments. Those with stronger ties to home governments can better access and leverage intergovernmental diplomatic connections, thus benefiting potentially from enhanced access to information, reduced political risks, and increased legitimacy. Such ability of politically connected firms is more useful where weak institutional impartiality in the host country inhibits neutral treatment of foreign investors. Empirically, using overseas investment location decisions by Chinese firms, we find that the types of home government ties (i.e., whether they are organizational or personal and whether those relationships are with central or local goverments) and the impartiality of host institutions are both important contingencies affecting firms’ utilization of diplomatic relations. We discuss the implications of our study to research on network theory, political ties, and internationalization of emerging market firms. 公司和政府在广阔的网络中运营,其中本国政府及其外交服务是公司和在外国地点的潜在合作伙伴之间的关键节点或“引荐点”。因此,国家之间的外交关系对外国投资地点的选择是重要的。使用网络视角,我们认为,良好的外交关系引导公司投资友好东道国的程度取决于它们与本国政府的政治联系。那些与本国政府有着更密切联系的公司可以更好地获得和利用政府间的外交关系,从而潜在地得益于增加的信息获取,减少的政治风险和增加的合法性。有政治关系公司的这种能力在脆弱的东道国制度公正性抑制对外国投资者的中立待遇的情况下更为有用。实证上,采用中国公司海外投资定位决策,我们发现,本国政府关系的类型(无论是组织上的还是个人的,无论是中央的还是地方政府的)和东道国制度公正性都是影响企业利用外交关系的重要的偶发事件。我们讨论我们的研究对网络理论,政治关系以及新兴市场公司国际化研究的启示。公司和政府在广阔的网络中运营,其中本国政府及其外交服务是公司和在外国地点的潜在合作伙伴之间的关键节点或“引荐点”。因此,国家之间的外交关系对外国投资地点的选择是重要的。使用网络视角,我们认为,良好的外交关系引导公司投资友好东道国的程度取决于它们与本国政府的政治联系。那些与本国政府有着更密切联系的公司可以更好地获得和利用政府间的外交关系,从而潜在地得益于增加的信息获取,减少的政治风险和增加的合法性。有政治关系公司的这种能力在脆弱的东道国制度公正性抑制对外国投资者的中立待遇的情况下更为有用。实证上,采用中国公司海外投资定位决策,我们发现,本国政府关系的类型(无论是组织上的还是个人的,无论是中央的还是地方政府的)和东道国制度公正性都是影响企业利用外交关系的重要的偶发事件。我们讨论我们的研究对网络理论,政治关系以及新兴市场公司国际化研究的启示