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61.
  • Arner, Peter, et al. (författare)
  • Dynamics of human adipose lipid turnover in health and metabolic disease
  • 2011
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 478:7367, s. 110-113
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Adipose tissue mass is determined by the storage and removal of triglycerides in adipocytes(1). Little is known, however, about adipose lipid turnover in humans in health and pathology. To study this in vivo, here we determined lipid age by measuring (14)C derived from above ground nuclear bomb tests in adipocyte lipids. We report that during the average ten-year lifespan of human adipocytes, triglycerides are renewed six times. Lipid age is independent of adipocyte size, is very stable across a wide range of adult ages and does not differ between genders. Adipocyte lipid turnover, however, is strongly related to conditions with disturbed lipid metabolism. In obesity, triglyceride removal rate (lipolysis followed by oxidation) is decreased and the amount of triglycerides stored each year is increased. In contrast, both lipid removal and storage rates are decreased in non-obese patients diagnosed with the most common hereditary form of dyslipidaemia, familial combined hyperlipidaemia. Lipid removal rate is positively correlated with the capacity of adipocytes to break down triglycerides, as assessed through lipolysis, and is inversely related to insulin resistance. Our data support a mechanism in which adipocyte lipid storage and removal have different roles in health and pathology. High storage but low triglyceride removal promotes fat tissue accumulation and obesity. Reduction of both triglyceride storage and removal decreases lipid shunting through adipose tissue and thus promotes dyslipidaemia. We identify adipocyte lipid turnover as a novel target for prevention and treatment of metabolic disease.</p>
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65.
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66.
  • Askarieh, Glareh, et al. (författare)
  • Self-assembly of spider silk proteins is controlled by a pH-sensitive relay
  • 2010
  • Ingår i: Nature. - Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 465, s. 236-U125
  • Tidskriftsartikel (refereegranskat)abstract
    • Nature's high-performance polymer, spider silk, consists of specific proteins, spidroins, with repetitive segments flanked by conserved non-repetitive domains(1,2). Spidroins are stored as a highly concentrated fluid dope. On silk formation, intermolecular interactions between repeat regions are established that provide strength and elasticity(3,4). How spiders manage to avoid premature spidroin aggregation before self-assembly is not yet established. A pH drop to 6.3 along the spider's spinning apparatus, altered salt composition and shear forces are believed to trigger the conversion to solid silk, but no molecular details are known. Miniature spidroins consisting of a few repetitive spidroin segments capped by the carboxy-terminal domain form metre-long silk-like fibres irrespective of pH(5). We discovered that incorporation of the amino-terminal domain of major ampullate spidroin 1 from the dragline of the nursery web spider Euprosthenops australis (NT) into mini-spidroins enables immediate, charge-dependent self-assembly at pH values around 6.3, but delays aggregation above pH7. The X-ray structure of NT, determined to 1.7 angstrom resolution, shows a homodimer of dipolar, antiparallel five-helix bundle subunits that lack homologues. The overall dimeric structure and observed charge distribution of NT is expected to be conserved through spider evolution and in all types of spidroins. Our results indicate a relay-like mechanism through which the N-terminal domain regulates spidroin assembly by inhibiting precocious aggregation during storage, and accelerating and directing self-assembly as the pH is lowered along the spider's silk extrusion duct.
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67.
  • Axelsson, Erik, et al. (författare)
  • The genomic signature of dog domestication reveals adaptation to a starch-rich diet
  • 2013
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 495:7441, s. 360-364
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>The domestication of dogs. was an important episode in the development of human civilization. The precise timing and location of this event is debated(1-5) and little is known about the genetic changes that accompanied the transformation of ancient wolves into domestic dogs. Here we conduct whole-genome resequencimg of dogs and wolves to identify 3.8 million genetic variants used to identify 36 genomic regions that probably represent targets for selection during dog domestication. Nineteen of these regions contain genes important in brain function, eight of which belong to nervous system development pathways and potentially underlie behavioural changes central to dog domestication(6). Ten genes with key roles in starch digestion and fat metabolism also show signals of selection. We identify candidate mutations in key genes and provide functional support for an increased starch digestion in dogs relative to wolves. Our results indicate that novel adaptations allowing the early ancestors of modern dogs to thrive on a diet rich in starch, relative to the carnivorous diet of wolves, constituted a crucial step in the early domestication of dogs.</p>
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68.
  • Azim, Eiman, et al. (författare)
  • Skilled reaching relies on a V2a propriospinal internal copy circuit
  • 2014
  • Ingår i: Nature. - Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7496, s. 357-363
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>The precision of skilled forelimb movement has long been presumed to rely on rapid feedback corrections triggered by internally directed copies of outgoing motor commands, but the functional relevance of inferred internal copy circuits has remained unclear. One class of spinal interneurons implicated in the control of mammalian forelimb movement, cervical propriospinal neurons (PNs), has the potential to convey an internal copy of premotor signals through dual innervation of forelimb-innervating motor neurons and precerebellar neurons of the lateral reticular nucleus. Here we examine whether the PN internal copy pathway functions in the control of goal-directed reaching. In mice, PNs include a genetically accessible subpopulation of cervical V2a interneurons, and their targeted ablation perturbs reaching while leaving intact other elements of forelimb movement. Moreover, optogenetic activation of the PN internal copy branch recruits a rapid cerebellar feedback loop that modulates forelimb motor neuron activity and severely disrupts reaching kinematics. Our findings implicate V2a PNs as the focus of an internal copy pathway assigned to the rapid updating of motor output during reaching behaviour.</p>
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69.
  • Aziz, Emad F., et al. (författare)
  • Interaction between liquid water and hydroxide revealed by core-hole de-excitation
  • 2008
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 455:7209, s. 89-91
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>The hydroxide ion plays an important role in many chemical and biochemical processes in aqueous solution(1). But ourmolecular- level understanding of its unusual and fast transport in water, and of the solvation patterns that allow fast transport, is far from complete. One proposal seeks to explain the properties and behaviour of the hydroxide ion by essentially regarding it as a water molecule that is missing a proton(2), and by inferring transport mechanisms and hydration structures from those of the excess proton. A competing proposal invokes instead unique and interchanging hydroxide hydration complexes, particularly the hypercoordinated OH-(H2O)(4) species and tri- coordinated OH-(H2O)(3) that can form a transient hydrogen bond between the H atom of the OH- and a neighbouring water molecule(3-5). Here we report measurements of core- level photoelectron emission and intermolecular Coulombic decay(6-8) for an aqueous hydroxide solution, which show that the hydrated hydroxide ion is capable of transiently donating a hydrogen bond to surrounding watermolecules. In agreement with recent experimental studies of hydroxide solutions(9-12), our finding thus supports the notion that the hydration structure of the hydroxide ion cannot be inferred from that of the hydrated excess proton.</p>
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70.
  • Babaev, Egor, et al. (författare)
  • A superconductor to superfluid phase transition in liquid metallic hydrogen
  • 2004
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 431:7009, s. 666-668
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Although hydrogen is the simplest of atoms, it does not form the simplest of solids or liquids. Quantum effects in these phases are considerable (a consequence of the light proton mass) and they have a demonstrable and often puzzling influence on many physical properties(1), including spatial order. To date, the structure of dense hydrogen remains experimentally elusive(2). Recent studies of the melting curve of hydrogen(3,4) indicate that at high (but experimentally accessible) pressures, compressed hydrogen will adopt a liquid state, even at low temperatures. In reaching this phase, hydrogen is also projected to pass through an insulator-to-metal transition. This raises the possibility of new state of matter: a near ground-state liquid metal, and its ordered states in the quantum domain. Ordered quantum fluids are traditionally categorized as superconductors or superfluids; these respective systems feature dissipationless electrical currents or mass flow. Here we report a topological analysis of the projected phase of liquid metallic hydrogen, finding that it may represent a new type of ordered quantum fluid. Specifically, we show that liquid metallic hydrogen cannot be categorized exclusively as a superconductor or superfluid. We predict that, in the presence of a magnetic field, liquid metallic hydrogen will exhibit several phase transitions to ordered states, ranging from superconductors to superfluids.</p>
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