Corneal avascularity is due to soluble VEGF receptor-1

Corneal avascularity-the absence of blood vessels in the cornea-is required for optical clarity and optimal vision, and has led to the cornea being widely used for validating pro- and anti-angiogenic therapeutic strategies for many disorders. But the molecular underpinnings of the avascular phenotype have until now remained obscure and are all the more remarkable given the presence in the cornea of vascular endothelial growth factor (VEGF)-A, a potent stimulator of angiogenesis, and the proximity of the cornea to vascularized tissues. Here we show that the cornea expresses soluble VEGF receptor-1 (sVEGFR-1; also known as sflt-1) and that suppression of this endogenous VEGF-A trap by neutralizing antibodies, RNA interference or Cre-lox-mediated gene disruption abolishes corneal avascularity in mice. The spontaneously vascularized corneas of corn1 and Pax6+/- mice and Pax6+/- patients with aniridia are deficient in sflt-1, and recombinant sflt-1 administration restores corneal avascularity in corn1 and Pax6+/- mice. Manatees, the only known creatures uniformly to have vascularized corneas, do not express sflt-1, whereas the avascular corneas of dugongs, also members of the order Sirenia, elephants, the closest extant terrestrial phylogenetic relatives of manatees, and other marine mammals (dolphins and whales) contain sflt-1, indicating that it has a crucial, evolutionarily conserved role. The recognition that sflt-1 is essential for preserving the avascular ambit of the cornea can rationally guide its use as a platform for angiogenic modulators, supports its use in treating neovascular diseases, and might provide insight into the immunological privilege of the cornea.     

Phenylethanolamine-N-methyl transferase activity in the ground squirrel (Citellus citellus)

Résumé L'activité de la phényléthanolamine-N-méthyltransférase (PNMT) a été mesurée dans l'homogénat des surrénales chez le Spermophile, soit actif, exposé aux températures extérieures de 20–25 °C ou de 6–8 °C, soit réveillé pendant l'hibernation. Chez les animaux actifs, l'effet du PNMT a été le plus faible. Une augmentation significative de l'activité enzymatique a été constatée chez les animaux actifs maintenus à la température de 6–8°C (p<0.001). L'activité du PNMT diminue immédiatement chez les Spermophiles réveillés pendant leur hibernation et ceci par rapport aux animaux actifs maintenus à la même température extérieure (p<0.01).     

Human dystrophin expression in mdx mice after intramuscular injection of DNA constructs

Duchenne's muscular dystrophy (DMD), which affects one in 3,500 males, causes progressive myopathy of skeletal and cardiac muscles and premature death. One approach to treatment would be to introduce the normal dystrophin gene into diseased muscle cells. When pure plasmid DNA is injected into rodent skeletal or cardiac muscle, the cells express reporter genes. We now show that a 12-kilobase full-length human dystrophin complementary DNA gene and a 6.3-kilobase Becker-like gene can be expressed in cultured cells and in vivo. When the human dystrophin expression plasmids are injected intramuscularly into dystrophin-deficient mdx mice, the human dystrophin proteins are present in the cytoplasm and sarcolemma of approximately 1% of the myofibres. Myofibres expressing human dystrophin contain an increased proportion of peripheral nuclei. The results indicate that transfer of the dystrophin gene into the myofibres of DMD patients could be beneficial, but a larger number of genetically modified myofibres will be necessary for clinical efficacy.     

How the Investor's Risk Preferences Influence the Optimal Allocation in a Credibilistic Portfolio Problem

A classical portfolio theory deals with finding the optimal proportion in which an agent invests a wealth in a risk-free asset and a probabilistic risky asset. Formulating and solving the problem depend on how the risk is represented and how, combined with the utility function defines a notion of expected utility. In this paper the risk is a fuzzy variable and the notion of expected utility is defined in the setting of Liu's credibility theory. Thus, the portfolio choice problem is formulated as an optimization problem in which the objective function is a credibilistic expected utility. Different approximation calculation formulas for the optimal allocation of the credibilistic risky asset are proved. These formulas contain two types of parameters: Various credibilistic moments associated with fuzzy variables(expected value, variance, skewness and kurtosis) and the risk aversion, prudence and temperance indicators of the utility function.     

An amorphous solid state of biogenic secondary organic aerosol particles

Secondary organic aerosol (SOA) particles are formed in the atmosphere from condensable oxidation products of anthropogenic and biogenic volatile organic compounds (VOCs). On a global scale, biogenic VOCs account for about 90% of VOC emissions and of SOA formation (90?billion kilograms of carbon per year). SOA particles can scatter radiation and act as cloud condensation or ice nuclei, and thereby influence the Earth's radiation balance and climate. They consist of a myriad of different compounds with varying physicochemical properties, and little information is available on the phase state of SOA particles. Gas-particle partitioning models usually assume that SOA particles are liquid, but here we present experimental evidence that they can be solid under ambient conditions. We investigated biogenic SOA particles formed from oxidation products of VOCs in plant chamber experiments and in boreal forests within a few hours after atmospheric nucleation events. On the basis of observed particle bouncing in an aerosol impactor and of electron microscopy we conclude that biogenic SOA particles can adopt an amorphous solid-most probably glassy-state. This amorphous solid state should provoke a rethinking of SOA processes because it may influence the partitioning of semi-volatile compounds, reduce the rate of heterogeneous chemical reactions, affect the particles' ability to accommodate water and act as cloud condensation or ice nuclei, and change the atmospheric lifetime of the particles. Thus, the results of this study challenge traditional views of the kinetics and thermodynamics of SOA formation and transformation in the atmosphere and their implications for air quality and climate.