Advances in the cellular and molecular biology of angiogenesis

Capillaries have been recognized for over a century as one of the most important components in regulating tissue oxygen transport, and their formation or angiogenesis a pivotal element of tissue remodelling during development and adaptation. Clinical interest stems from observations that both excessive and inadequate vascular growth plays a major role in human diseases, and novel developments in treatments for cancer and eye disease increasingly rely on anti-angiogenic therapies. Although the discovery of VEGF (vascular endothelial growth factor) provided the first clue for specificity of signalling in endothelial cell activation, understanding the integrative response that drives angiogenesis requires a much broader perspective. The Advances in the Cellular and Molecular Biology of Angiogenesis meeting brought together researchers at the forefront of this rapidly moving field to provide an update on current understanding, and the most recent insights into molecular and cellular mechanisms of vascular growth. The plenary lecture highlighted the integrative nature of the angiogenic process, whereas invited contributions from basic and clinician scientists described fundamental mechanisms and disease-associated issues of blood vessel formation, grouped under a number of themes to aid discussion. These articles will appeal to academic, clinical and pharmaceutical scientists interested in the molecular and cellular basis of angiogenesis, their modulation or dysfunction in human diseases, and application of these findings towards translational medicine.     

Isolation of a diploid, apomictic plant of Hieracium aurantiacum

 As in most taxa that contain gametophytic apomicts, all of the apomictic biotypes studied so far in the genus Hieracium subgenus Pilosella have been recorded as polyploids. As part of a study of variation in apomictically derived populations of H. aurantiacum, a diploid plant was identified. Apospory, the mechanism of apomixis typically observed in this taxon, was observed in this plant. Unreduced megagametophytes at various developmental stages were commonly observed in the developing ovules, and endosperm formation was autonomous. The eventual seed set, however, was low. This appears to have been due to the proliferation of competing megagametophytes and embryos within each ovule. Pollen sterility was also observed, primarily resulting from the dysfunction of microgametogenesis at the uninucleate stage. Received: 3 September 1996 / Revision accepted: 21 March 1997     

Inference of Low and High-Grade Glioma Gene Regulatory Networks Delineates the Role of Rnd3 in Establishing Multiple Hallmarks of Cancer

Gliomas are a highly heterogeneous group of brain tumours that are refractory to treatment, highly invasive and pro-angiogenic. Glioblastoma patients have an average survival time of less than 15 months. Understanding the molecular basis of different grades of glioma, from well differentiated, low-grade tumours to high-grade tumours, is a key step in defining new therapeutic targets. Here we use a data-driven approach to learn the structure of gene regulatory networks from observational data and use the resulting models to formulate hypothesis on the molecular determinants of glioma stage. Remarkably, integration of available knowledge with functional genomics datasets representing clinical and pre-clinical studies reveals important properties within the regulatory circuits controlling low and high-grade glioma. Our analyses first show that low and high-grade gliomas are characterised by a switch in activity of two subsets of Rho GTPases. The first one is involved in maintaining normal glial cell function, while the second is linked to the establishment of multiple hallmarks of cancer. Next, the development and application of a novel data integration methodology reveals novel functions of RND3 in controlling glioma cell migration, invasion, proliferation, angiogenesis and clinical outcome.     

The importance of novel and agricultural habitats for the avifauna of an oceanic island

Conservation management can no longer rely on protecting pristine habitats, but must consider the wider landscape. This is especially true on oceanic islands where endemic species are believed to be particularly susceptible to the extinction risks that accompany land conversion. Despite this, there is a paucity of studies examining how endemic communities on oceanic islands may be distributed across such human-modified habitats. Taking Príncipe Island in West Africa as a case study, we investigate how avian communities vary across the habitats (primary forest, secondary forest, agricultural areas) of this globally important centre of endemism. Here, recent policy reforms aimed at poverty alleviation and increased food production are rapidly altering the current land-use mosaic. Across all habitats, 27 bird species were encountered. Survey points in secondary forest and agricultural areas were, on average, more diverse and held higher overall abundances of birds than those within primary forest. This was true for both the entire avian assemblage and the endemic species alone. Nevertheless, two IUCN-listed species were restricted to primary forest, and many other endemics occurred at higher densities within this habitat. We demonstrate that agricultural areas and novel habitats, such as secondary forest, can hold high abundances of endemic species and thus have the potential to act as a resource for biodiversity conservation. A double-stranded approach to conservation is therefore required that both protects the integrity of the primary forest and controls the rapid changes in agricultural land-use to ensure that it continues to support a large component of the endemic avifauna.     

A spectral study of cobalt(II)-substituted Bacillus cereus phospholipase C

The coordination sphere of both the structural and catalytic zinc ions of Bacillus cereus phospholipase C has been probed by substitution of cobalt(II) for zinc and investigation of the resultant derivatives by a variety of spectroscopic techniques. The electronic absorption, circular dichroic, magnetic circular dichroic, and electron paramagnetic resonance spectra were found to be strikingly similar when cobalt(II) was substituted into either site and are consistent with a distorted octahedral environment for the metal ion in both sites. Octahedral coordination appears comparatively rare in zinc metalloenzymes but has been suggested for glyoxalase I [Sellin, S., Eriksson, L. E. G., Aronsson, A.-C., & Mannervik, B. (1983) J. Biol. Chem. 258, 2091-2093; Garcia-Iniguez, L., Powers, L., Chance, B., Sellin, S., Mannervik, B., & Mildvan, A. S. (1984) Biochemistry 23, 685-689], transcarboxylase [Fung, C.-H., Mildvan, A. S., & Leigh, J. S. (1974) Biochemistry 13, 1160-1169], and the regulatory binding site of Aeromonas aminopeptidase [Prescott, J. M., Wagner, F. W., Holmquist, B., & Vallee, B. L. (1985) Biochemistry 24, 5350-5356]. Phospholipase C is so far unique in having two such sites.     

The human chromosome content in human x rodent somatic cell hybrids analyzed by a screening technique using Alu PCR

The ubiquitous nature of the Alu sequence throughout the human genome forms the basis of an assay we present here for analyzing the human chromosome content of human x rodent somatic cell hybrids. A human-specific Alu primer was used both to amplify sequences and to 32P label the products in a polymerase chain reaction (PCR) technique. Unlabeled inter-Alu PCR products from two series of human x rodent hybrids were used to prepare dot blots which were probed with labeled inter-Alu products prepared from between 10(3) and 10(4) hybrid cells. In the first series we demonstrate that a labeled inter-Alu probe from the hybrid DL18ts, containing a single chromosome 18, on a dot blot hybridized only with those inter-Alu products containing chromosome 18. Similar specificity for human chromosome 5 was shown when a Southern blot of the PCR products was hybridized with a probe made from the hybrid HHW 213, which contains only chromosome 5p. Using a dot blot from a second series of control hybrids, 15 of which contained single human chromosomes, hybridization of a labeled probe from the hybrid 18X4-1 was shown to react specifically with the controls that expressed chromosome 18. Application of the technique reported here allows simple and rapid characterization of the human chromosome content in human x rodent hybrids.