Mutually Supportive Mechanisms of Inflammation and Vascular Remodeling.

Chronic inflammation is often accompanied by angiogenesis, the development of new blood vessels from existing ones. This vascular response is a response to chronic hypoxia and/or ischemia, but is also contributory to the progression of disorders including atherosclerosis, arthritis, and tumor growth. Proinflammatory and proangiogenic mediators and signaling pathways form a complex and interrelated network in these conditions, and many factors exert multiple effects. Inflammation drives angiogenesis by direct and indirect mechanisms, promoting endothelial proliferation, migration, and vessel sprouting, but also by mediating extracellular matrix remodeling and release of sequestered growth factors, and recruitment of proangiogenic leukocyte subsets. The role of inflammation in promoting angiogenesis is well documented, but by facilitating greater infiltration of leukocytes and plasma proteins into inflamed tissues, angiogenesis can also propagate chronic inflammation. This review examines the mutually supportive relationship between angiogenesis and inflammation, and considers how these interactions might be exploited to promote resolution of chronic inflammatory or angiogenic disorders.

Syndecan proteoglycan contributions to cytoskeletal organization and contractility.

Cells exert tension on the extracellular matrix through specific receptors that link to the actin cytoskeleton. The best characterized are the integrins, which, when activated and clustered, can link to the extracellular matrix at specialized adhesion zones, known as focal contacts or focal adhesions. However, other transmembrane receptors can also localize there, including one transmembrane proteoglycan, syndecan-4. This heparan sulfate proteoglycan can also link directly to the cytoskeleton through alpha-actinin, and can signal through protein kinase C. In turn, the pathway leads to RhoA and Rho kinases that control actomyosin contractility. Syndecan-4 may, therefore, be a sensor of tension exerted on the matrix. These processes are described here, their significance being potential roles in wound contraction, tumor-stroma interactions, fibrosis and the regulation of motility.

Syndecan signaling: when, where and why?

Syndecans are the only family of transmembrane heparan sulphate proteoglycans. Invertebrates all appear to have one Syndecan core protein, but in mammals there are four. Examination of the core protein sequences shows that the cytoplasmic domains are the most conserved. This suggests that Syndecans make important interactions and/or signalling contributions. It has been established that all syndecans can interact with proteins of the actin-associated cytoskeleton, but details of signalling have been harder to ascertain. However, it appears that Syndecans can signal, primarily to the cytoskeleton, and the details are reviewed here. Only for vertebrate syndecan-4 is there substantial detail, and it remains a challenge to dissect the functions and signalling of other vertebrate and invertebrate syndecans.

The hydrophobin HCf-1 of Cladosporium fulvum is required for efficient water-mediated dispersal of conidia.

Six hydrophobin genes (HCf-1 to -6) have thus far been identified in the tomato pathogen Cladosporium fulvum. HCf-1 to -4 are Class I hydrophobins and HCf-5 and -6 are Class II hydrophobins. In this paper we describe the isolation of deletion mutants that lack HCf-1, HCf-2, or both these genes. Global down-regulation of the expression of Class I hydrophobins is achieved by homology-dependent gene silencing. Analysis of the mutant strains shows that HCf-1 confers hydrophilic character to the conidia and this facilitates the dissemination of conidia on the surface of water droplets. Other Class I hydrophobins, such as HCf-3 or HCf-4, may be involved in the development and germination of conidia.

Genetic diversity in Proteus mirabilis isolates found in the urinary tract of rheumatoid arthritis patients.

OBJECTIVE: Elevated levels of anti-Proteus antibodies but not antibodies to E. coli have been reported in patients with rheumatoid arthritis (RA). The suggestion has been made that P. mirabilis may have a role in the aetiopathogenesis of rheumatoid arthritis. The aim of this study was to determine whether there are differences at the genetic level inisolates of P. mirabilis obtained from controls and RA patients. METHODS: A blind study was performed whereby P. mirabilis isolates obtained from urinary cultures of RA patients and controls were analysed using RAPD PCR. Isolates were then grouped on the basis of their DNA band profile after agarose gel electrophoresis, thereby allowing the composition of the Proteus population in the urinary tract to be analysed at the genetic level. RESULTS: Fourteen different DNA band profiles were obtained from the 93 isolates tested: 70% of these isolates fell into only five of the 14 groups and approximately 25% of all isolates fell into one group. No differences were observed in the frequency of isolates from either control or RA subjects. CONCLUSIONS: There is genetic diversity in P. mirabilis populations found in the urinary tract, but there are no differences in the frequency of these bacteria between RA patients and controls.

The molecular genetics of cultivated mushrooms.

The types, economic significance and methods of production of the principal cultivated mushrooms are described in outline. These organisms are all less than ideal for conventional genetic analysis and breeding, so molecular methods afford a particular opportunity to advance our understanding of their biology and potentially give the prospect of improvement by gene manipulation. The sequences described are limited to those found in GenBank by August 1999. The gene sequences isolated from the white button mushroom Agaricus bisporus, the shiitake Lentinula edodes, the oyster mushrooms Pleurotus spp., the paddy straw mushroom Volvariella volvacea and the enotake Flammulina velutipes are described. The largest group are genes from A. bisporus, which includes 29 for intracellular proteins and 12 for secreted proteins. In comparison, only a total of 26 sequences can be reported for the other cultivated species. A. bisporus is also the only cultivated species for which molecular karyotyping is already supported by reliable markers for all 13 of its chromosomes.