Keratinocyte growth factor

Keratinocyte growth factor (KGF) is a member of the heparin-binding fibroblast growth factor family (FGF-7) with a distinctive pattern of target-cell specificity. Studies performed in cell culture suggested that KGF was mitogenically active only on epithelial cells, albeit from a variety of tissues. In contrast, KGF was produced solely by cells of mesenchymal origin, leading to the hypothesis that it might function as a paracrine mediator of mesenchymal-epithelial communication. Biochemical analysis and molecular cloning established that the KGF receptor (KGFR) was a tyrosine kinase isoform encoded by the fgfr-2 gene. Many detailed investigations of KGF and KGFR expression in whole tissue and cell lines largely substantiated the pattern initially perceived in vitro of mesenchymal and epithelial distribution, respectively. Moreover, functional assays in organ culture and in vivo and studies of KGF regulation by sex sterorid hormones reinforced the idea that KGF acts predominantly on epithelial cells to elicit a variety of responses including proliferation, migration and morphogenesis.     

The effect of rainfall on tick challenge at Kyle Recreational Park,Zimbabwe

The effect of rainfall pattern on tick challenge was investigated at Kyle Recreational Park, Zimbabwe, from 1991 to 1992 using drag and removal plot methods to sample environmental tick density. The abundance of adults and nymphs of the brown ear-tick Rhipicephalus appendiculatus and larvae of the bont tick Amblyomma hebraeum was positively correlated with monthly rainfall, whereas no relationship with rainfall was revealed for larval R. appendiculatus, adults of the red-legged tick R. evertsi, or larvae of the blue tick Boophilus decoloratus. A comparison between 1991 (490 mm rainfall) and the drought year of 1992 (161 mm) revealed significant differences in the abundance of R. appendiculatus, A. hebraeum, and B. decoloratus. During the wet season, R. appendiculatus adults were 2–3 time more numerous in the environment during the higher rainfall year of 1991. A. hebraeum larval abundance exhibited a similar pattern to that of R. appendiculatus adults, but B. decoloratus larvae were more abundant in the drought year of 1992 during both the wet and dry seasons. Comparable tick abundance data collected at Kyle during the above-average rainfall years of 1975–1977 (mean = 1029 mm) were compared with tick challenge during the below-average rainfall years of 1991–1992 (mean = 326 mm). In grassland sand habitat and all habitats combined R. appendiculatus adults, nymphs, and larvae were much more abundant during the high rainfall years. In contrast, larvae of B. decoloratus were more numerous during the drier years. A. hebraeum larvae were also more abundant during the drier years. The strong positive correlation of adult R. appendiculatus abundance with rainfall and the coincidence of increased adult tick challenge with increased rainfall indicates that adult R. appendiculatus tick burden on hosts would be heaviest during the wet season and high rainfall years.     

Influence of redox potential on the anaerobic biotransformation of nitrogen-heterocyclic compounds in anoxic freshwater sediments

The potential for degradation of four nitrogen-heterocyclic compounds was investigated in fresh-water sediment slurries maintained under denitrifying, sulfate-reducing, and methanogenic conditions. Pyridine (10 mg/l) was rapidly transformed within 4 weeks under denitrifying conditions but persisted for up to 3 months under sulfate-reducing and methanogenic conditions. No intermediate biotransformation products of pyridine metabolism were detected under denitrifying conditions. Quinoline (10 mg/l) was completely transformed without a lag phase under methanogenic and sulfate-reducing conditions after incubation for 23 and 45 days, respectively. 2-Hydroxyquinoline was produced concomitantly with quinoline transformation under methanogenic and sulfate-reducing conditions. Under denitrifying conditions, less than 23% of the initial concentration of quinoline was transformed after anaerobic incubation for 83 days. Indole, however, was completely removed from sediment slurries under denitrifying, sulfate-reducing, and methanogenic conditions after anaerobic incubation for 18, 27, and 17 days, respectively. Only low amounts of oxindole (2–4 mg/l) accumulated during indole metabolism under methanogenic and denitrifying conditions, but under sulfate-reducing conditions, oxindole accumulation was stoichiometric with indole transformation. No evidence for biotransformation of carbazole was noted for all anaerobic conditions tested.     

The advantage of long-distance clonal spreading in highly disturbed habitats

Summary Classical theory states that cover of annual plants should increase relative to perennials as disturbance frequency increases. However, it has been suggested that long-distance clonal spreading can allow some perennial plants to survive in highly disturbed areas by quickly spreading into disturbed patches. To evaluate these hypotheses, we analysed data of plant distributions in two different ecosystems, a barrier island and a short-grass steppe. The disturbances studied were sand deposition during storms (overwash) on the barrier island and grazing by cattle in the short-grass steppe. In each case the disturbance frequency varied over the ecosystem; we categorized different areas in terms of their disturbance frequencies. All plant species in each area were categorized as one of four plant life forms (1) annual or biennial, (2) herbaceous perennial without long-distance clonal spreading (3) herbaceous perennial with long-distance clonal spreading (i.e guerilla form) and (4) woody plant. Percentage cover of each plant life form in each disturbance frequency category was calculated. In both ecosystems, (1) there was an increase in the relative cover of annuals as one moved from areas of low to moderate disturbance frequencies, but then a decrease in cover of annuals as one moved into the areas of highest disturbance frequency and (2) the guerilla forms showed the greatest relative increase in cover from moderately to highly disturbed areas. The combination of two factors can explain this pattern: (1) long-distance clonal spreading effectively reduces the time to colonization of recently disturbed sites and (2) effects of the disturbances in these two systems are probably more severe for seeds than for stems. We illustrate these effects using a spatially explicit simulation model of the population dynamics of plants in a disturbed landscape.     

Floral evolution and male reproductive success: Optimal dispensing schedules for pollen dispersal by animal-pollinated plants

Summary Selection favouring an outcrossing plant's ability to sire seeds generally promotes floral characters that increase (1) the frequency of pollinator visits, (2) the number of pollen grains dispersed to other plants by each pollinator and (3) the probability of a pollen grain successfully fertilizing an ovule after reaching a stigma. Flowers influence pollen dispersal and fertilization probabilities by determining the pattern of pollen removal during a series of visits (dispensing schedule). We model male reproductive success to identify optimal dispensing schedules, which characteristically involve monotonic increases in the proportion of remaining pollen removed during successive visits. These schedules balance the benefits of restricted removal, which counteracts the diminishing returns associated with animal pollination (e.g. pollinator grooming, local mate competition), with the advantages of increased removal to avoid time-dependent losses in fertilization ability (e.g. pollen precedence, declining viability). Because pollinator availability mediates this balance, the most effective dispensing schedule allows dynamic adjustment of removal to the prevailing frequency of visits experienced by individual plants. As an example of such dynamic removal we demonstrate that the dispensing mechanism ofLupinus sericeus flowers allows facultative adjustment of removal to the interval between visits. Because optimal control of pollen removal can increase a plant's mating opportunities by an order of magnitude, dispensing mechanisms should be a common component of floral design.     

Mapping initiation sites for simian virus 40 DNA synthesis events in vitro.

Primer RNA-DNA, a small (approximately 30-nucleotide) RNA-DNA hybrid molecule, was identified in recent studies of simian virus 40 DNA synthesis in vitro. The available evidence indicates that primer RNA-DNA is the product of the polymerase alpha-primase complex. Primer RNA-DNA is formed exclusively on lagging-strand DNA templates; it is synthesized initially in the vicinity of the simian virus 40 origin and at later times at sites progressively distal to the origin. To further characterize initiation events, template sequences encoding the 5' ends of both primer RNA and primer DNA, formed during a 5-s pulse, have been determined. Analyses of these sequences demonstrate the existence of an initiation signal for lagging-strand synthesis. At any given position, the initiation signal is located within those template sequences encoding primer RNA, situated proximal to the nucleotide encoding the 5' end of the RNA primer. In most instances, the sequence 5'-TTN-3' (where N encodes the nucleotide at the 5' end of the primer) is a feature of the initiation signal. Initiation signals are present, on average, once every 19 nucleotides. These results are discussed in terms of the mechanism of Okazaki fragment formation and possible links between prokaryotic and eukaryotic initiation events.     

Ubiquitous and tenacious methylation of the CpG site in codon 248 of the p53 gene may explain its frequent appearance as a mutational hot spot in human cancer.

Cytosine methylation at CpG dinucleotides is thought to cause more than one-third of all transition mutations responsible for human genetic diseases and cancer. We investigated the methylation status of the CpG dinucleotide at codon 248 in exon 7 of the p53 gene because this codon is a hot spot for inactivating mutations in the germ line and in most human somatic tissues examined. Codon 248 is contained within an HpaII site (CCGG), and the methylation status of this and flanking CpG sites was analyzed by using the methylation-sensitive enzymes CfoI (GCGC) and HpaII. Codon 248 and the CfoI and HpaII sites in the flanking introns were methylated in every tissue and cell line examined, indicating extensive methylation of this region in the p53 gene. Exhaustive treatment of an osteogenic sarcoma cell line, TE85, with the hypomethylating drug 5-aza-2'-deoxycytidine did not demethylate codon 248 or the CfoI sites in intron 6, although considerable global demethylation of the p53 gene was induced. Constructs containing either exon 7 alone or exon 7 and the flanking introns were transfected into TE85 cells to determine whether de novo methylation would occur. The presence of exon 7 alone caused some de novo methylation to occur at codon 248. More extensive de novo methylation of the CfoI sites in intron 6, which contains an Alu sequence, occurred in cells transfected with a vector containing exon 7 and flanking introns. With longer time in culture, there was increased methylation at the CfoI sites, and de novo methylation of codon 248 and its flanking HpaII sites was observed. These de novo-methylated sites were also resistant to 5-aza-2'-deoxycytidine-induced demethylation. The frequent methylation of codon 248 and adjacent Alu sequence may explain the enhanced mutability of this site as a result of the deamination of the 5-methylcytosine.