319 research outputs found

    Naar een integraal alcoholbeleid in België

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    The omnipresence and social acceptance of alcohol in Belgium in many cases masks the harmful effects of alcohol. In order to reduce the negative consequences of harmful alcohol consumption, much research has been done in recent years into the effectiveness of possible policy measures. Despite the recommendations of these studies and of several health organizations, there is still no national alcohol policy plan in force in Belgium. Measures in the areas of prevention, care, price, supply and marketing are necessary to effectively reduce the harmful effects of alcohol.De alomtegenwoordigheid en sociale aanvaarding van alcohol in België verbloemt in vele gevallen de schadelijke gevolgen die alcohol heeft. Om die gevolgen te reduceren, is er de afgelopen jaar veel onderzoek gedaan naar de effectiviteit van mogelijke overheidsmaatregelen. Onder andere de Wereldgezondheidsorganisatie adviseert landen over effectieve beleidsmaatregelen op basis van wetenschappelijke inzichten. Ondanks de aanbevelingen van de Wereldgezondheidsorganisatie en uit wetenschappelijke onderzoeken is er in België nog altijd geen sprake van een nationaal alcoholbeleidsplan waarin deze maatregelen integraal zijn opgenomen. Maatregelen op het vlak van preventie, hulpverlening, prijs, aanbod en marketing zijn noodzakelijk om de schadelijke gevolgen van alcohol effectief te reduceren

    Model Protocells from Single-Chain Lipids

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    Significant progress has been made in the construction of laboratory models of protocells. Most frequently the developed vesicle systems utilize single-chain lipids rather than the double-chain lipids typically found in biological membranes. Although single-chain lipids yield less robust vesicles, their dynamic characteristics are highly exploitable for protocellular functions. Herein the advantages of using single-chain lipids in the construction of protocells are discussed

    Two approaches to the study of the origin of life.

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    This paper compares two approaches that attempt to explain the origin of life, or biogenesis. The more established approach is one based on chemical principles, whereas a new, yet not widely known approach begins from a physical perspective. According to the first approach, life would have begun with - often organic - compounds. After having developed to a certain level of complexity and mutual dependence within a non-compartmentalised organic soup, they would have assembled into a functioning cell. In contrast, the second, physical type of approach has life developing within tiny compartments from the beginning. It emphasises the importance of redox reactions between inorganic elements and compounds found on two sides of a compartmental boundary. Without this boundary, ÂżlifeÂż would not have begun, nor have been maintained; this boundary - and the complex cell membrane that evolved from it - forms the essence of life

    The compositional and evolutionary logic of metabolism

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    Metabolism displays striking and robust regularities in the forms of modularity and hierarchy, whose composition may be compactly described. This renders metabolic architecture comprehensible as a system, and suggests the order in which layers of that system emerged. Metabolism also serves as the foundation in other hierarchies, at least up to cellular integration including bioenergetics and molecular replication, and trophic ecology. The recapitulation of patterns first seen in metabolism, in these higher levels, suggests metabolism as a source of causation or constraint on many forms of organization in the biosphere. We identify as modules widely reused subsets of chemicals, reactions, or functions, each with a conserved internal structure. At the small molecule substrate level, module boundaries are generally associated with the most complex reaction mechanisms and the most conserved enzymes. Cofactors form a structurally and functionally distinctive control layer over the small-molecule substrate. Complex cofactors are often used at module boundaries of the substrate level, while simpler ones participate in widely used reactions. Cofactor functions thus act as "keys" that incorporate classes of organic reactions within biochemistry. The same modules that organize the compositional diversity of metabolism are argued to have governed long-term evolution. Early evolution of core metabolism, especially carbon-fixation, appears to have required few innovations among a small number of conserved modules, to produce adaptations to simple biogeochemical changes of environment. We demonstrate these features of metabolism at several levels of hierarchy, beginning with the small-molecule substrate and network architecture, continuing with cofactors and key conserved reactions, and culminating in the aggregation of multiple diverse physical and biochemical processes in cells.Comment: 56 pages, 28 figure

    Bootstrapping the energy flow in the beginning of life.

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    This paper suggests that the energy flow on which all living structures depend only started up slowly, the low-energy, initial phase starting up a second, slightly more energetic phase, and so on. In this way, the build up of the energy flow follows a bootstrapping process similar to that found in the development of computers, the first generation making possible the calculations necessary for constructing the second one, etc. In the biogenetic upstart of an energy flow, non-metals in the lower periods of the Periodic Table of Elements would have constituted the most primitive systems, their operation being enhanced and later supplanted by elements in the higher periods that demand more energy. This bootstrapping process would put the development of the metabolisms based on the second period elements carbon, nitrogen and oxygen at the end of the evolutionary process rather than at, or even before, the biogenetic even

    On the Free Energy That Drove Primordial Anabolism

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    A key problem in understanding the origin of life is to explain the mechanism(s) that led to the spontaneous assembly of molecular building blocks that ultimately resulted in the appearance of macromolecular structures as they are known in modern biochemistry today. An indispensable thermodynamic prerequisite for such a primordial anabolism is the mechanistic coupling to processes that supplied the free energy required. Here I review different sources of free energy and discuss the potential of each form having been involved in the very first anabolic reactions that were fundamental to increase molecular complexity and thus were essential for life

    Molecular Etiology of Atherogenesis – In Vitro Induction of Lipidosis in Macrophages with a New LDL Model

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    BACKGROUND: Atherosclerosis starts by lipid accumulation in the arterial intima and progresses into a chronic vascular inflammatory disease. A major atherogenic process is the formation of lipid-loaded macrophages in which a breakdown of the endolysomal pathway results in irreversible accumulation of cargo in the late endocytic compartments with a phenotype similar to several forms of lipidosis. Macrophages exposed to oxidized LDL exihibit this phenomenon in vitro and manifest an impaired degradation of internalized lipids and enhanced inflammatory stimulation. Identification of the specific chemical component(s) causing this phenotype has been elusive because of the chemical complexity of oxidized LDL. METHODOLOGY/PRINCIPAL FINDINGS: Lipid "core aldehydes" are formed in oxidized LDL and exist in atherosclerotic plaques. These aldehydes are slowly oxidized in situ and (much faster) by intracellular aldehyde oxidizing systems to cholesteryl hemiesters. We show that a single cholesteryl hemiester incorporated into native, non-oxidized LDL induces a lipidosis phenotype with subsequent cell death in macrophages. Internalization of the cholesteryl hemiester via the native LDL vehicle induced lipid accumulation in a time- and concentration-dependent manner in "frozen" endolysosomes. Quantitative shotgun lipidomics analysis showed that internalized lipid in cholesteryl hemiester-intoxicated cells remained largely unprocessed in those lipid-rich organelles. CONCLUSIONS/SIGNIFICANCE: The principle elucidated with the present cholesteryl hemiester-containing native-LDL model, extended to other molecular components of oxidized LDL, will help in defining the molecular etiology and etiological hierarchy of atherogenic agents
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