49 research outputs found

    Vesicular and non-vesicular transport feed distinct glycosylation pathways in the Golgi.

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    Newly synthesized proteins and lipids are transported across the Golgi complex via different mechanisms whose respective roles are not completely clear. We previously identified a non-vesicular intra-Golgi transport pathway for glucosylceramide (GlcCer)--the common precursor of the different series of glycosphingolipids-that is operated by the cytosolic GlcCer-transfer protein FAPP2 (also known as PLEKHA8) (ref. 1). However, the molecular determinants of the FAPP2-mediated transfer of GlcCer from the cis-Golgi to the trans-Golgi network, as well as the physiological relevance of maintaining two parallel transport pathways of GlcCer--vesicular and non-vesicular--through the Golgi, remain poorly defined. Here, using mouse and cell models, we clarify the molecular mechanisms underlying the intra-Golgi vectorial transfer of GlcCer by FAPP2 and show that GlcCer is channelled by vesicular and non-vesicular transport to two topologically distinct glycosylation tracks in the Golgi cisternae and the trans-Golgi network, respectively. Our results indicate that the transport modality across the Golgi complex is a key determinant for the glycosylation pattern of a cargo and establish a new paradigm for the branching of the glycosphingolipid synthetic pathwa

    Clinical practice guidelines of the European Association for Endoscopic Surgery (EAES) on bariatric surgery: update 2020 endorsed by IFSO-EC, EASO and ESPCOP

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    Background: Surgery for obesity and metabolic diseases has been evolved in the light of new scientific evidence, long-term outcomes and accumulated experience. EAES has sponsored an update of previous guidelines on bariatric surgery. Methods: A multidisciplinary group of bariatric surgeons, obesity physicians, nutritional experts, psychologists, anesthetists and a patient representative comprised the guideline development panel. Development and reporting conformed to GRADE guidelines and AGREE II standards. Results: Systematic review of databases, record selection, data extraction and synthesis, evidence appraisal and evidence-to-decision frameworks were developed for 42 key questions in the domains Indication; Preoperative work-up; Perioperative management; Non-bypass, bypass and one-anastomosis procedures; Revisional surgery; Postoperative care; and Investigational procedures. A total of 36 recommendations and position statements were formed through a modified Delphi procedure. Conclusion: This document summarizes the latest evidence on bariatric surgery through state-of-the art guideline development, aiming to facilitate evidence-based clinical decisions

    Biochemical Characterization of a CDC6-like Protein from the Crenarchaeon Sulfolobus solfataricus

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    Vascular inflammation and endothelial dysfunction in experimental hypertension

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    Essential hypertension is characterized by increased peripheral vascular resistance to blood flow. The endothelium is a crucial regulator of vascular tone. Its function is impaired in patients with hypertension, with reduced vasodilation, increased vascular tone associated with a proinflammatory and prothrombotic state. Low-grade inflammation localized in vascular tissue is therefore recognized as an important contributor to the pathophysiology of hypertension, to the initiation and progression of atherosclerosis as well as to the development of cardiovascular diseases. © 2011 Carmine Savoia et al

    Modular organization of the Sulfolobus solfataricus mini-chromosome maintenance protein

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    Rapid microbial response to the presence of an ancient relic in the Antarctic Dry Valleys

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    The extreme cold and aridity of the Antarctic McMurdo Dry Valleys have led to the longstanding belief that metabolic rates of soil microbiota are negligible, and that ecosystem changes take place over millennia. Here we report the first direct experimental evidence that soil microbial communities undergo rapid and lasting changes in response to contemporary environmental conditions. Mummified seals, curious natural artifacts found scattered throughout Dry Valleys, alter their underlying soil environment by stabilizing temperatures, elevating relative humidity and reducing ultraviolet exposure. In a unique, multi-year mummified seal transplantation experiment, we found that endemic Dry Valley microbial communities responded to these changes within 3 years, resulting in a sevenfold increase in CO2 flux and a significant reduction in biodiversity. These findings challenge prevailing ideas about Antarctic Dry Valley ecosystems and indicate that current and future environmental conditions may strongly influence the ecology of the dominant biota in the Dry Valleys
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