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Ambati BK Nozaki M Singh N Takeda A Jani PD Suthar T Albuquerque RJ Richter E Sakurai E Newcomb MT Kleinman ME Caldwell RB Lin Q Ogura Y Orecchia A Samuelson DA Agnew DW St Leger J Green WR Mahasreshti PJ Curiel DT Kwan D Marsh H Ikeda S Leiper LJ Collinson JM Bogdanovich S Khurana TS Shibuya M Baldwin ME Ferrara N Gerber HP De Falco S Witta J Baffi JZ Raisler BJ Ambati J 《Nature》2006,443(7114):993-997
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. 相似文献
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Torrelles JM Patel NA Gómez JF Ho PT Rodríguez LF Anglada G Garay G Greenhill L Curiel S Cantó J 《Nature》2001,411(6835):277-280
The exact processes by which interstellar matter condenses to form young stars are of great interest, in part because they bear on the formation of planets like our own from the material that fails to become part of the star. Theoretical models suggest that ejection of gas during early phases of stellar evolution is a key mechanism for removing excess angular momentum, thereby allowing material to drift inwards towards the star through an accretion disk. Such ejections also limit the mass that can be accumulated by the stellar core. To date, these ejections have been observed to be bipolar and highly collimated, in agreement with theory. Here we report observations at very high angular resolution of the proper motions of an arc of water-vapour masers near a very young, massive star in Cepheus. We find that the arc of masers can be fitted to a circle with an accuracy of one part in a thousand, and that the structure is expanding. Only a sphere will always produce a circle in projection, so our observations strongly suggest that the perfectly spherical ejection of material from this star took place about 33 years earlier. The spherical symmetry of the ejecta and its episodic nature are very surprising in the light of present theories. 相似文献
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Patel NA Curiel S Sridharan TK Zhang Q Hunter TR Ho PT Torrelles JM Moran JM Gómez JF Anglada G 《Nature》2005,437(7055):109-111
The processes leading to the birth of low-mass stars such as our Sun have been well studied, but the formation of high-mass (over eight times the Sun's mass, M(o)) stars remains poorly understood. Recent studies suggest that high-mass stars may form through accretion of material from a circumstellar disk, in essentially the same way as low-mass stars form, rather than through the merging of several low-mass stars. There is as yet, however, no conclusive evidence. Here we report the presence of a flattened disk-like structure around a massive 15M(o) protostar in the Cepheus A region, based on observations of continuum emission from the dust and line emission from the molecular gas. The disk has a radius of about 330 astronomical units (Au) and a mass of 1 to 8 M(o). It is oriented perpendicular to, and spatially coincident with, the central embedded powerful bipolar radio jet, just as is the case with low-mass stars, from which we conclude that high-mass stars can form through accretion. 相似文献
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