Induction of tumors in mice by genomic hypomethylation

Genome-wide DNA hypomethylation occurs in many human cancers, but whether this epigenetic change is a cause or consequence of tumorigenesis has been unclear. To explore this phenomenon, we generated mice carrying a hypomorphic DNA methyltransferase 1 (Dnmt1) allele, which reduces Dnmt1 expression to 10% of wild-type levels and results in substantial genome-wide hypomethylation in all tissues. The mutant mice were runted at birth, and at 4 to 8 months of age they developed aggressive T cell lymphomas that displayed a high frequency of chromosome 15 trisomy. These results indicate that DNA hypomethylation plays a causal role in tumor formation, possibly by promoting chromosomal instability.     

Requirement for activin A and transforming growth factor--beta 1 pro-regions in homodimer assembly

Many proteins are initially synthesized as part of a large precursor. The role of the pro-region in the biosynthesis of transforming growth factor--beta 1 (TGF-beta 1) and activin A, two structurally related disulfide-linked homodimers synthesized as large precursors, was studied. Vectors that expressed either the pro-region or the mature regions of these molecules were used in complementation experiments, only when the pro-region was coexpressed with the mature region did intracellular dimerization and secretion of biologically active homodimers occur. The pro-regions of activin A and TGF-beta 1, therefore, aid the folding, disulfide bond formation, and export of their respective homodimers.     

The use of soil data in natural heritage planning and management

Abstract. Native woodland restoration is a conservation priority within the UK and there is an increasing awareness that a long-term strategy is required to guide this process. A GIS-based modelling approach has been developed, which links site conditions as expressed in an integrated soil and land cover dataset with the site requirements for different woodland types. There are three important aspects to the model – the parameter weightings, the added value of the integrated dataset, and the woodland categories which are described and predicted. The initial quantitative and qualitative validation has been encouraging although more is required and planned. The results indicate that for broad strategic planning purposes, predictions of woodland potential are not improved significantly when climatic factors are incorporated. The concept that soil acts as an integrator of other environmental variables is discussed alongside the practical application of the model by a range of users.     

Chemotherapy of Babesia divergens in the gerbil, Meriones unguiculatus

It was found that surprisingly low doses of four babesicides were effective against Babesia divergens in gerbils and it was concluded that this was due to the involvement of host resistance, which may be of a non-specific nature. The efficacy of the drugs relative to each other was the same in gerbils as in cattle and this host-parasite system is evidently more suitable for the screening of babesicides than are other rodent babesia systems. The prophylactic dose of imidocarb dipropionate required to provide a similar degree of protection in gerbils as in cattle was found to be much higher and was very close to toxic levels. Challenge infections resulted in sterile immunity. Acute babesiosis in gerbils could be cured with all four drugs if parasitaemias were below approximately 45 per cent and packed cell volumes above 18 per cent at treatment.     

Models based on weather for the development phases of the sheep tick, ixodes ricinus L.

The epidemiology of tick-transmitted disease cannot be understood until those factors considered important to the life-cycle of the tick are properly investigated. Existing experimental results on the development of different stages of the tick life-cycle have been examined with a view to obtaining biological development rates for the purpose of predicting development under field conditions where temperature fluctuates. Field studies carried out in Ireland have enabled the predicted development times to be compared with those observed for several stages of the tick life-cycle. It is hoped that the models presented will clarify the importance or otherwise of climate to tick development and explore the potential of formulating a successful prediction system for tick activity. Ultimately such a system should aid control of tick-transmitted diseases.