VEGF regulates haematopoietic stem cell survival by an internal autocrine loop mechanism

Vascular endothelial growth factor (VEGF) is a principal regulator of blood vessel formation and haematopoiesis, but the mechanisms by which VEGF differentially regulates these processes have been elusive. Here we describe a regulatory loop by which VEGF controls survival of haematopoietic stem cells (HSCs). We observed a reduction in survival, colony formation and in vivo repopulation rates of HSCs after ablation of the VEGF gene in mice. Intracellularly acting small-molecule inhibitors of VEGF receptor (VEGFR) tyrosine kinase dramatically reduced colony formation of HSCs, thus mimicking deletion of the VEGF gene. However, blocking VEGF by administering a soluble VEGFR-1, which acts extracellularly, induced only minor effects. These findings support the involvement in HSC survival of a VEGF-dependent internal autocrine loop mechanism (that is, the mechanism is resistant to inhibitors that fail to penetrate the intracellular compartment). Not only ligands selective for VEGF and VEGFR-2 but also VEGFR-1 agonists rescued survival and repopulation of VEGF-deficient HSCs, revealing a function for VEGFR-1 signalling during haematopoiesis.     

A gravitationally lensed quasar with quadruple images separated by 14.62 arcseconds

Gravitational lensing is a powerful tool for the study of the distribution of dark matter in the Universe. The cold-dark-matter model of the formation of large-scale structures (that is, clusters of galaxies and even larger assemblies) predicts the existence of quasars gravitationally lensed by concentrations of dark matter so massive that the quasar images would be split by over 7 arcsec. Numerous searches for large-separation lensed quasars have, however, been unsuccessful. All of the roughly 70 lensed quasars known, including the first lensed quasar discovered, have smaller separations that can be explained in terms of galaxy-scale concentrations of baryonic matter. Although gravitationally lensed galaxies with large separations are known, quasars are more useful cosmological probes because of the simplicity of the resulting lens systems. Here we report the discovery of a lensed quasar, SDSS J1004 + 4112, which has a maximum separation between the components of 14.62 arcsec. Such a large separation means that the lensing object must be dominated by dark matter. Our results are fully consistent with theoretical expectations based on the cold-dark-matter model.     

A class of compact dwarf galaxies from disruptive processes in galaxy clusters

Dwarf galaxies have attracted increased attention in recent years, because of their susceptibility to galaxy transformation processes within rich galaxy clusters. Direct evidence for these processes, however, has been difficult to obtain, with a small number of diffuse light trails and intra-cluster stars being the only signs of galaxy disruption. Furthermore, our current knowledge of dwarf galaxy populations may be very incomplete, because traditional galaxy surveys are insensitive to extremely diffuse or compact galaxies. Aware of these concerns, we recently undertook an all-object survey of the Fornax galaxy cluster. This revealed a new population of compact members, overlooked in previous conventional surveys. Here we demonstrate that these 'ultra-compact' dwarf galaxies are structurally and dynamically distinct from both globular star clusters and known types of dwarf galaxy, and thus represent a new class of dwarf galaxy. Our data are consistent with the interpretation that these are the remnant nuclei of disrupted dwarf galaxies, making them an easily observed tracer of galaxy disruption.     

The Ehrenfest Classification of Phase Transitions: Introduction and Evolution

The first classification of general types of transition between phases of matter, introduced by Paul Ehrenfest in 1933, lies at a crossroads in the thermodynamical study of critical phenomena. It arose following the discovery in 1932 of a suprising new phase transition in liquid helium, the “lambda transition,” when W. H. Keesom and coworkers in Leiden, Holland observed a λhaped “jump” discontinuity in the curve giving the temperature dependence of the specific heat of helium at a critical value. This apparent jump led Ehrenfest to introduce a classification of phase transitions on the basis of jumps in derivatives of the free energy function. This classification was immediately applied by A.J. Rutgers to the study of the transition from the normal to superconducting state in metals. Eduard Justi and Max von Laue soon questioned the possibility of its class of “second-order phase transitions” -- of which the “lambda transition was believed to be the arche type -- but C.J. Gorter and H.B.G. Casimir used an “order parameter to demonstrate their existence in superconductors. As a crossroads of study, the Ehrenfest classification was forced to undergo a slow, adaptive evolution during subsequent decades. During the 1940s the classification was increasingly used in discussions of liquid-gas, order-disorder, paramagnetic-ferromagnetic and normal-super-conducting phase transitions. Already in 1944 however, Lars Onsagers solution of the Ising model for two-dimensional magnets was seen to possess a derivative with a logarithmic divergence rather than a jump as the critical point was approached. In the 1950s, experiments further revealed the lambda transition in helium to exhibit similar behavior. Rather than being a prime example of an Ehrenfest phase transition, the lambda transition was seen to lie outside the Ehrenfest classification. The Ehrenfest scheme was then extended to include such singularities, most notably by A. Brain Pippard in 1957, with widespread acceptance. During the 1960s these logarithmic infinities were the focus of the investigation of “scaling” by Leo Kadanoff, B. Widom and others. By the 1970s, a radically simplified binary classification of phase transitions into “first-order” and “continuous” transitions was increasingly adopted.     

Summer habitat use and selection by female Sage Grouse ( Centrocercus urophasianus ) in Oregon

Cover types and vegetative characteristics (e.g., grasses, forbs, shrubs) used by female Sage Grouse ( Centrocercus urophasianus ) during summer were compared with available habitat on two study areas in southeastern Oregon. Broodless hens, which constituted 114 of the 125 (91%) radio-marked hens studied, selected big ( Artemisia tridentata ) subspp.) and low sagebrush ( A. arbuscular ) cover types at both study areas. At Hart Mountain, broodless hens did not select specific vegetative characteristics within cover types. However, at Jackass Creek, forb cover was greater ( P = .004) at broodless hen sites than at random locations. Differences in habitat use by broodless hens between study areas were associated with differences in forb availability. Broodless hens used a greater diversity of cover types than hens with broods. Broodless hens gathered in flocks and remained separate from but near hens with broods during early summer. By early July broodless hens moved to meadows while hens with broods remained in upland habitats.     

Insertion of DNA sequences into the human chromosomal beta-globin locus by homologous recombination

A 'rescuable' plasmid containing globin gene sequences allowing recombination with homologous chromosomal sequences has enabled us to produce, score and clone mammalian cells with the plasmid integrated into the human beta-globin locus. The planned modification was achieved in about one per thousand transformed cells whether or not the target gene was expressed.