106 research outputs found
Cosmogenic Radioactivities in the Peace River and Harleton Chondrites
Comparison of activity ratios of radioactive nuclide in old and newly-fallen chondrite
Carcinogenic Effects in a Phenylketonuria Mouse Model
Phenylketonuria (PKU) is a metabolic disorder caused by impaired phenylalanine hydroxylase (PAH). This condition results in hyperphenylalaninemia and elevated levels of abnormal phenylalanine metabolites, among which is phenylacetic acid/phenylacetate (PA). In recent years, PA and its analogs were found to have anticancer activity against a variety of malignancies suggesting the possibility that PKU may offer protection against cancer through chronically elevated levels of PA. We tested this hypothesis in a genetic mouse model of PKU (PAHenu2) which has a biochemical profile that closely resembles that of human PKU. Plasma levels of phenylalanine in homozygous (HMZ) PAHenu2 mice were >12-fold those of heterozygous (HTZ) littermates while tyrosine levels were reduced. Phenylketones, including PA, were also markedly elevated to the range seen in the human disease. Mice were subjected to 7,12 dimethylbenz[a]anthracene (DMBA) carcinogenesis, a model which is sensitive to the anticancer effects of the PA derivative 4-chlorophenylacetate (4-CPA). Tumor induction by DMBA was not significantly different between the HTZ and HMZ mice, either in total tumor development or in the type of cancers that arose. HMZ mice were then treated with 4-CPA as positive controls for the anticancer effects of PA and to evaluate its possible effects on phenylalanine metabolism in PKU mice. 4-CPA had no effect on the plasma concentrations of phenylalanine, phenylketones, or tyrosine. Surprisingly, the HMZ mice treated with 4-CPA developed an unexplained neuromuscular syndrome which precluded its use in these animals as an anticancer agent. Together, these studies support the use of PAHenu2 mice as a model for studying human PKU. Chronically elevated levels of PA in the PAHenu2 mice were not protective against cancer
Shaping the growth behaviour of biofilms initiated from bacterial aggregates
Bacterial biofilms are usually assumed to originate from individual cells
deposited on a surface. However, many biofilm-forming bacteria tend to
aggregate in the planktonic phase so that it is possible that many natural and
infectious biofilms originate wholly or partially from pre-formed cell
aggregates. Here, we use agent-based computer simulations to investigate the
role of pre-formed aggregates in biofilm development. Focusing on the initial
shape the aggregate forms on the surface, we find that the degree of spreading
of an aggregate on a surface can play an important role in determining its
eventual fate during biofilm development. Specifically, initially spread
aggregates perform better when competition with surrounding unaggregated
bacterial cells is low, while initially rounded aggregates perform better when
competition with surrounding unaggregated cells is high. These contrasting
outcomes are governed by a trade-off between aggregate surface area and height.
Our results provide new insight into biofilm formation and development, and
reveal new factors that may be at play in the social evolution of biofilm
communities
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