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  • Journal article
    Lorenzoni L, Belloni A, Sassi F, 2014,

    Health-care expenditure and health policy in the USA versus other high-spending OECD countries

    , The Lancet, Vol: 384, Pages: 83-92, ISSN: 0140-6736

    The USA has exceptional levels of health-care expenditure, but growth has slowed dramatically in recent years, amidst major efforts to close the coverage gap with other countries of the Organisation for Economic Co-operation and Development (OECD). We reviewed expenditure trends and key policies since 2000 in the USA and five other high-spending OECD countries. Higher health-sector prices explain much of the difference between the USA and other high-spending countries, and price dynamics are largely responsible for the slowdown in expenditure growth. Other high-spending countries did not face the same coverage challenges, and could draw from a broader set of policies to keep expenditure under control, but expenditure growth was similar to the USA. Tightening Medicare and Medicaid price controls on plans and providers, and leveraging the scale of the public programmes to increase efficiency in financing and care delivery, might prevent a future economic recovery from offsetting the slowdown in health sector prices and expenditure growth.

  • Journal article
    O'Donnelly K, Zhao G, Patel P, Butt MS, Mak LH, Kretschmer S, Woscholski R, Barter LMCet al., 2014,

    Isolation and kinetic characterisation of hydrophobically distinct populations of form I Rubisco

    , Planet Methods, Vol: 10, ISSN: 1746-4811

    BackgroundRubisco (Ribulose-1,5-bisphosphate carboxylase/oxygenase) is a Calvin Cycle enzyme involved in CO2 assimilation. It is thought to be a major cause of photosynthetic inefficiency, suffering from both a slow catalytic rate and lack of specificity due to a competing reaction with oxygen. Revealing and understanding the engineering rules that dictate Rubisco’s activity could have a significant impact on photosynthetic efficiency and crop yield.ResultsThis paper describes the purification and characterisation of a number of hydrophobically distinct populations of Rubisco from both Spinacia oleracea and Brassica oleracea extracts. The populations were obtained using a novel and rapid purification protocol that employs hydrophobic interaction chromatography (HIC) as a form I Rubisco enrichment procedure, resulting in distinct Rubisco populations of expected enzymatic activities, high purities and integrity.ConclusionsWe demonstrate here that HIC can be employed to isolate form I Rubisco with purities and activities comparable to those obtained via ion exchange chromatography (IEC). Interestingly, and in contrast to other published purification methods, HIC resulted in the isolation of a number of hydrophobically distinct Rubisco populations. Our findings reveal a so far unaccounted diversity in the hydrophobic properties within form 1 Rubisco. By employing HIC to isolate and characterise Spinacia oleracea and Brassica oleracea, we show that the presence of these distinct Rubisco populations is not species specific, and we report for the first time the kinetic properties of Rubisco from Brassica oleracea extracts. These observations may aid future studies concerning Rubisco’s structural and functional properties.

  • Journal article
    Frost G, Sleeth ML, Sahuri-Arisoylu M, Lizarbe B, Cerdan S, Brody L, Anastasovska J, Ghourab S, Hankir M, Zhang S, Carling D, Swann JR, Gibson G, Viardot A, Morrison D, Thomas EL, Bell JDet al., 2014,

    The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism

    , Nature Communications, Vol: 5, Pages: 1-11, ISSN: 2041-1723

    Increased intake of dietary carbohydrate that is fermented in the colon by the microbiota has been reported to decrease body weight, although the mechanism remains unclear. Here we use in vivo11C-acetate and PET-CT scanning to show that colonic acetate crosses the blood–brain barrier and is taken up by the brain. Intraperitoneal acetate results in appetite suppression and hypothalamic neuronal activation patterning. We also show that acetate administration is associated with activation of acetyl-CoA carboxylase and changes in the expression profiles of regulatory neuropeptides that favour appetite suppression. Furthermore, we demonstrate through 13C high-resolution magic-angle-spinning that 13C acetate from fermentation of 13C-labelled carbohydrate in the colon increases hypothalamic 13C acetate above baseline levels. Hypothalamic 13C acetate regionally increases the 13C labelling of the glutamate–glutamine and GABA neuroglial cycles, with hypothalamic 13C lactate reaching higher levels than the ‘remaining brain’. These observations suggest that acetate has a direct role in central appetite regulation.

  • Journal article
    Martorell O, Merlos-Suarez A, Campbell K, Barriga FM, Christov CP, Miguel-Aliaga I, Batlle E, Casanova J, Casali Aet al., 2014,

    Conserved Mechanisms of Tumorigenesis in the Drosophila Adult Midgut

    , PLOS One, Vol: 9, ISSN: 1932-6203

    Whereas the series of genetic events leading to colorectal cancer (CRC) have been well established, the precise functionsthat these alterations play in tumor progression and how they disrupt intestinal homeostasis remain poorly characterized.Activation of the Wnt/Wg signaling pathway by a mutation in the gene APC is the most common trigger for CRC, inducingbenign lesions that progress to carcinomas due to the accumulation of other genetic alterations. Among those, Rasmutations drive tumour progression in CRC, as well as in most epithelial cancers. As mammalian and Drosophila’s intestinesshare many similarities, we decided to explore the alterations induced in the Drosophila midgut by the combined activationof the Wnt signaling pathway with gain of function of Ras signaling in the intestinal stem cells. Here we show thatcompound Apc-Ras clones, but not clones bearing the individual mutations, expand as aggressive intestinal tumor-likeoutgrowths. These lesions reproduce many of the human CRC hallmarks such as increased proliferation, blockade of celldifferentiation and cell polarity and disrupted organ architecture. This process is followed by expression of tumoral markerspresent in human lesions. Finally, a metabolic behavioral assay shows that these flies suffer a progressive deterioration inintestinal homeostasis, providing a simple readout that could be used in screens for tumor modifiers or therapeuticcompounds. Taken together, our results illustrate the conservation of the mechanisms of CRC tumorigenesis in Drosophila,providing an excellent model system to unravel the events that, upon mutation in Apc and Ras, lead to CRC initiation andprogression.

  • Journal article
    Linneweber GA, Jacobson J, Busch KE, Hudry B, Christov CP, Dormann D, Yuan M, Otani T, Knust E, de Bono M, Miguel-Aliaga Iet al., 2014,

    Neuronal control of metabolism through nutrient-dependent modulation of tracheal branching

    , Cell, Vol: 156, Pages: 69-83, ISSN: 0092-8674

    During adaptive angiogenesis, a key process in the etiology and treatment of cancer and obesity, the vasculature changes to meet the metabolic needs of its target tissues. Although the cues governing vascular remodeling are not fully understood, target-derived signals are generally believed to underlie this process. Here, we identify an alternative mechanism by characterizing the previously unrecognized nutrient-dependent plasticity of the Drosophila tracheal system: a network of oxygen-delivering tubules developmentally akin to mammalian blood vessels. We find that this plasticity, particularly prominent in the intestine, drives—rather than responds to—metabolic change. Mechanistically, it is regulated by distinct populations of nutrient- and oxygen-responsive neurons that, through delivery of both local and systemic insulin- and VIP-like neuropeptides, sculpt the growth of specific tracheal subsets. Thus, we describe a novel mechanism by which nutritional cues modulate neuronal activity to give rise to organ-specific, long-lasting changes in vascular architecture.

  • Journal article
    Herforth A, Frongillo EA, Sassi F, Mclean MS, Arabi M, Tirado C, Remans R, Mantilla G, Thomson M, Pingali Pet al., 2014,

    Toward an integrated approach to nutritional quality, environmental sustainability, and economic viability: research and measurement gaps

    , GLOBAL RESEARCH AGENDA FOR NUTRITION SCIENCE, Vol: 1332, Pages: 1-21, ISSN: 0077-8923
  • Journal article
    Sarraf-Zadeh L, Christen S, Sauer U, Cognigni P, Miguel-Aliaga I, Stocker H, Koehler K, Hafen Eet al., 2013,

    Local requirement of the <i>Drosophila</i> insulin binding protein imp-L2 in coordinating developmental progression with nutritional conditions

    , DEVELOPMENTAL BIOLOGY, Vol: 381, Pages: 97-106, ISSN: 0012-1606
  • Journal article
    Devaux M, Sassi F, 2013,

    Social inequalities in obesity and overweight in 11 OECD countries

    , EUROPEAN JOURNAL OF PUBLIC HEALTH, Vol: 23, Pages: 464-469, ISSN: 1101-1262
  • Journal article
    Mohammed MAP, Tarleton E, Charalambides MN, Williams JGet al., 2013,

    Mechanical characterization and micromechanical modeling of bread dough

    , JOURNAL OF RHEOLOGY, Vol: 57, Pages: 249-272, ISSN: 0148-6055
  • Journal article
    Lemaitre B, Miguel-Aliaga I, 2013,

    The Digestive Tract of <i>Drosophila melanogaster</i>

    , ANNUAL REVIEW OF GENETICS, VOL 47, Vol: 47, Pages: 377-404, ISSN: 0066-4197

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