39 research outputs found
Fast growth associated with aberrant vasculature and hypoxia in fibroblast growth factor 8b (FGF8b) over-expressing PC-3 prostate tumour xenografts
Background: Prostate tumours are commonly poorly oxygenated which is associated with tumour progression and development of resistance to chemotherapeutic drugs and radiotherapy. Fibroblast growth factor 8b (FGF8b) is a mitogenic and angiogenic factor, which is expressed at an increased level in human prostate tumours and is associated with a poor prognosis. We studied the effect of FGF8b on tumour oxygenation and growth parameters in xenografts in comparison with vascular endothelial growth factor (VEGF)-expressing xenografts, representing another fast growing and angiogenic tumour model. Methods: Subcutaneous tumours of PC-3 cells transfected with FGF8b, VEGF or empty (mock) vectors were produced and studied for vascularity, cell proliferation, glucose metabolism and oxygenation. Tumours were evaluated by immunohistochemistry (IHC), flow cytometry, use of radiolabelled markers of energy metabolism ([F-18] FDG) and hypoxia ([F-18] EF5), and intratumoral polarographic measurements of pO(2). Results: Both FGF8b and VEGF tumours grew rapidly in nude mice and showed highly vascularised morphology. Perfusion studies, pO(2) measurements, [F-18] EF5 and [F-18] FDG uptake as well as IHC staining for glucose transport protein (GLUT1) and hypoxia inducible factor (HIF) 1 showed that VEGF xenografts were well-perfused and oxygenised, as expected, whereas FGF8b tumours were as hypoxic as mock tumours. These results suggest that FGF8b-induced tumour capillaries are defective. Nevertheless, the growth rate of hypoxic FGF8b tumours was highly increased, as that of well-oxygenised VEGF tumours, when compared with hypoxic mock tumour controls. Conclusion: FGF8b is able to induce fast growth in strongly hypoxic tumour microenvironment whereas VEGF-stimulated growth advantage is associated with improved perfusion and oxygenation of prostate tumour xenografts
The Promoter of the Cereal VERNALIZATION1 Gene Is Sufficient for Transcriptional Induction by Prolonged Cold
The VERNALIZATION1 (VRN1) gene of temperate cereals is transcriptionally activated by prolonged cold during winter (vernalization) to promote flowering. To investigate the mechanisms controlling induction of VRN1 by prolonged cold, different regions of the VRN1 gene were fused to the GREEN FLUORESCENT PROTEIN (GFP) reporter and expression of the resulting gene constructs was assayed in transgenic barley (Hordeum vulgare). A 2 kb segment of the promoter of VRN1 was sufficient for GFP expression in the leaves and shoot apex of transgenic barley plants. Fluorescence increased at the shoot apex prior to inflorescence initiation and was subsequently maintained in the developing inflorescence. The promoter was also sufficient for low-temperature induction of GFP expression. A naturally occurring insertion in the proximal promoter, which is associated with elevated VRN1 expression and early flowering in some spring wheats, did not abolish induction of VRN1 transcription by prolonged cold, however. A translational fusion of the promoter and transcribed regions of VRN1 to GFP, VRN1::GFP, was localised to nuclei of cells at the shoot apex of transgenic barley plants. The distribution of VRN1::GFP at the shoot apex was similar to the expression pattern of the VRN1 promoter-GFP reporter gene. Fluorescence from the VRN1::GFP fusion protein increased in the developing leaves after prolonged cold treatment. These observations suggest that the promoter of VRN1 is targeted by mechanisms that trigger vernalization-induced flowering in economically important temperate cereal crops
Interspecific variation in the relationship between clutch size, laying date and intensity of urbanization in four species of hole-nesting birds
The increase in size of human populations in urban and agricultural areas has
resulted in considerable habitat conversion globally. Such anthropogenic areas
have specific environmental characteristics, which influence the physiology, life
history, and population dynamics of plants and animals. For example, the date
of bud burst is advanced in urban compared to nearby natural areas. In some
birds, breeding success is determined by synchrony between timing of breeding
and peak food abundance. Pertinently, caterpillars are an important food source
for the nestlings of many bird species, and their abundance is influenced by
environmental factors such as temperature and date of bud burst. Higher temperatures
and advanced date of bud burst in urban areas could advance peak
caterpillar abundance and thus affect breeding phenology of birds. In order to
test whether laying date advance and clutch sizes decrease with the intensity of
urbanization, we analyzed the timing of breeding and clutch size in relation to
intensity of urbanization as a measure of human impact in 199 nest box plots
across Europe, North Africa, and the Middle East (i.e., the Western Palearctic)
for four species of hole-nesters: blue tits (Cyanistes caeruleus), great tits (Parus
major), collared flycatchers (Ficedula albicollis), and pied flycatchers (Ficedula
hypoleuca). Meanwhile, we estimated the intensity of urbanization as the density
of buildings surrounding study plots measured on orthophotographs. For the
four study species, the intensity of urbanization was not correlated with laying
date. Clutch size in blue and great tits does not seem affected by the intensity
of urbanization, while in collared and pied flycatchers it decreased with increasing
intensity of urbanization. This is the first large-scale study showing a species-
specific major correlation between intensity of urbanization and the
ecology of breeding. The underlying mechanisms for the relationships between
life history and urbanization remain to be determined. We propose that effects
of food abundance or quality, temperature, noise, pollution, or disturbance by
humans may on their own or in combination affect laying date and/or clutch
size