Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes

In obesity and type 2 diabetes, expression of the GLUT4 glucose transporter is decreased selectively in adipocytes. Adipose-specific Glut4 (also known as Slc2a4) knockout (adipose-Glut4(-/-)) mice show insulin resistance secondarily in muscle and liver. Here we show, using DNA arrays, that expression of retinol binding protein-4 (RBP4) is elevated in adipose tissue of adipose-Glut4(-/-) mice. We show that serum RBP4 levels are elevated in insulin-resistant mice and humans with obesity and type 2 diabetes. RBP4 levels are normalized by rosiglitazone, an insulin-sensitizing drug. Transgenic overexpression of human RBP4 or injection of recombinant RBP4 in normal mice causes insulin resistance. Conversely, genetic deletion of Rbp4 enhances insulin sensitivity. Fenretinide, a synthetic retinoid that increases urinary excretion of RBP4, normalizes serum RBP4 levels and improves insulin resistance and glucose intolerance in mice with obesity induced by a high-fat diet. Increasing serum RBP4 induces hepatic expression of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK) and impairs insulin signalling in muscle. Thus, RBP4 is an adipocyte-derived 'signal' that may contribute to the pathogenesis of type 2 diabetes. Lowering RBP4 could be a new strategy for treating type 2 diabetes.     

Neurosphere-derived multipotent precursors promote neuroprotection by an immunomodulatory mechanism

In degenerative disorders of the central nervous system (CNS), transplantation of neural multipotent (stem) precursor cells (NPCs) is aimed at replacing damaged neural cells. Here we show that in CNS inflammation, NPCs are able to promote neuroprotection by maintaining undifferentiated features and exerting unexpected immune-like functions. In a mouse model of chronic CNS inflammation, systemically injected adult syngeneic NPCs use constitutively activated integrins and functional chemokine receptors to selectively enter the inflamed CNS. These undifferentiated cells survive repeated episodes of CNS inflammation by accumulating within perivascular areas where reactive astrocytes, inflamed endothelial cells and encephalitogenic T cells produce neurogenic and gliogenic regulators. In perivascular CNS areas, surviving adult NPCs induce apoptosis of blood-borne CNS-infiltrating encephalitogenic T cells, thus protecting against chronic neural tissue loss as well as disease-related disability. These results indicate that undifferentiated adult NPCs have relevant therapeutic potential in chronic inflammatory CNS disorders because they display immune-like functions that promote long-lasting neuroprotection.     

The genome of the protist parasite Entamoeba histolytica

Entamoeba histolytica is an intestinal parasite and the causative agent of amoebiasis, which is a significant source of morbidity and mortality in developing countries. Here we present the genome of E. histolytica, which reveals a variety of metabolic adaptations shared with two other amitochondrial protist pathogens: Giardia lamblia and Trichomonas vaginalis. These adaptations include reduction or elimination of most mitochondrial metabolic pathways and the use of oxidative stress enzymes generally associated with anaerobic prokaryotes. Phylogenomic analysis identifies evidence for lateral gene transfer of bacterial genes into the E. histolytica genome, the effects of which centre on expanding aspects of E. histolytica's metabolic repertoire. The presence of these genes and the potential for novel metabolic pathways in E. histolytica may allow for the development of new chemotherapeutic agents. The genome encodes a large number of novel receptor kinases and contains expansions of a variety of gene families, including those associated with virulence. Additional genome features include an abundance of tandemly repeated transfer-RNA-containing arrays, which may have a structural function in the genome. Analysis of the genome provides new insights into the workings and genome evolution of a major human pathogen.     

Collapse of stiff conjugated polymers with chemical defects into ordered, cylindrical conformations

The optical, electronic and mechanical properties of synthetic and biological materials consisting of polymer chains depend sensitively on the conformation adopted by these chains. The range of conformations available to such systems has accordingly been of intense fundamental as well as practical interest, and distinct conformational classes have been predicted, depending on the stiffness of the polymer chains and the strength of attractive interactions between segments within a chain. For example, flexible polymers should adopt highly disordered conformations resembling either a random coil or, in the presence of strong intrachain attractions, a so-called 'molten globule'. Stiff polymers with strong intrachain interactions, in contrast, are expected to collapse into conformations with long-range order, in the shape of toroids or rod-like structures. Here we use computer simulations to show that the anisotropy distribution obtained from polarization spectroscopy measurements on individual poly[2-methoxy-5-(2'-ethylhexyl)oxy-1,4-phenylenevinylene] polymer molecules is consistent with this prototypical stiff conjugated polymer adopting a highly ordered, collapsed conformation that cannot be correlated with ideal toroid or rod structures. We find that the presence of so-called 'tetrahedral chemical defects', where conjugated carbon-carbon links are replaced by tetrahedral links, divides the polymer chain into structurally identifiable quasi-straight segments that allow the molecule to adopt cylindrical conformations. Indeed, highly ordered, cylindrical conformations may be a critical factor in dictating the extraordinary photophysical properties of conjugated polymers, including highly efficient intramolecular energy transfer and significant local optical anisotropy in thin films.     

A correlation of the ionization energies of water and ethers with the polar and inductive substituent constants

Résumé On démontre que les énergies d'ionisation des ethers, R₂O, sont une fonction linéaire des constantes substituentes polaires et inductives. Les groupes alkyls qui donnent des électrons abaissent l'énergie d'ionisation du «lone-pair» de l'atome d'oxygène. L'eau est inclue dans la corrélation de même que lether le plus simple. On trouve qu'avec bonne approximationE _I =10,00+ 2,57 ^* ouE _I =12,59+28,0 _I .     

Les glycoprotéines sériques dans le granulome expérimental provoqué par la carrageenine

Summary We studied serum glycoproteins in rats and guinea pigs during the development of granulomas, provoked by carrageenin injection. In rats total serum sialic acid was raised as well as sialic acid soluble in sulfosalicylic acid and haptoglobin. The rise of these 2 fractions, seromucoid and haptoglobine accounts quantitatively for the rise of the total sialic acid. In guinea pigs total serum sialic acid was unchanged, but sulfosalicylosoluble sialic acid as well as haptoglobin were much higher than basal values. Quantitatively the serum glycoprotein reaction was much higher in rats than in guinea pigs.     

Human sex-linked muscular dystrophy: Kinetics of the isometric twitch

Résumé Les propriétés mécaniques du muscle adducteur du pouce atteint de dystrophie musculaire de type Duchenne ont été étudiées in situ chez 15 malades. La force produite par la secousse isométrique et le tétanos isométrique est réduite dans tous les cas. Le temps de contraction de la secousse isométrique et son temps de relaxation sont légèrement supérieurs aux valeurs de contrôle. Cette différence disparait au cours de la stimulation répétée du nerf à 2/sec. Ces observations montrent que l'activité ATPase de la myosine (déterminant la vitesse de contraction) et le processus de séquestration du Ca⁺⁺ myoplasmique dans le réticulum sarcoplasmique (déterminant la vitesse de relaxation) ne sont pas altérés de façon irréversible dans la dystrophie musculaire de Duchenne.

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On leave from the Neurology Clinic of the Medical Academy, Warsaw.

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This work was supported by the Muscular Dystrophy Associations of America Inc. and by the Fonds de la Recherche Scientifique Médicale.     

Diethylpyrocarbonate interferes with lipid-protein interaction and glucose transport in the human red cell membrane

Summary Diethylpyrocarbonate largely diminishes both discontinuities in red cell glucose transport and also in red cell membrane ANS fluorescence at about 17–20°C.We are very much indebted to Dr K.-H. Röhm for valuable discussions of this paper. This work was supported by the Deutsche Forschungsgemeinschaft.