University of Wales

About: University of Wales is a education organization based out in Cardiff, United Kingdom. It is known for research contribution in the topics: Population & Poison control. The organization has 12462 authors who have published 16873 publications receiving 700173 citations. The organization is also known as: Prifysgol Cymru.

Translocation and gross deletion breakpoints in human inherited disease and cancer I: Nucleotide composition and recombination‐associated motifs

Abstract: Translocations and gross deletions are important causes of both cancer and inherited disease. Such gene rearrangements are nonrandomly distributed in the human genome as a consequence of selection for growth advantage and/or the inherent potential of some DNA sequences to be frequently involved in breakage and recombination. Using the Gross Rearrangement Breakpoint Database [GRaBD; www.uwcm.ac.uk/uwcm/mg/grabd/grabd.html] (containing 397 germ-line and somatic DNA breakpoint junction sequences derived from 219 different rearrangements underlying human inherited disease and cancer), we have analyzed the sequence context of translocation and deletion breakpoints in a search for general characteristics that might have rendered these sequences prone to rearrangement. The oligonucleotide composition of breakpoint junctions and a set of reference sequences, matched for length and genomic location, were compared with respect to their nucleotide composition. Deletion breakpoints were found to be AT-rich whereas by comparison, translocation breakpoints were GC-rich. Alternating purine-pyrimidine sequences were found to be significantly over-represented in the vicinity of deletion breakpoints while polypyrimidine tracts were over-represented at translocation breakpoints. A number of recombination-associated motifs were found to be over-represented at translocation breakpoints (including DNA polymerase pause sites/frameshift hotspots, immunoglobulin heavy chain class switch sites, heptamer/nonamer V(D)J recombination signal sequences, translin binding sites, and the chi element) but, with the exception of the translin-binding site and immunoglobulin heavy chain class switch sites, none of these motifs were over-represented at deletion breakpoints. Alu sequences were found to span both breakpoints in seven cases of gross deletion that may thus be inferred to have arisen by homologous recombination. Our results are therefore consistent with a role for homologous unequal recombination in deletion mutagenesis and a role for nonhomologous recombination in the generation of translocations.

The Ethical Demand

Abstract: The previous chapter gave us some reasons for caution about speaking of trust as a pervasive aspect of all social life. However, I wish now to turn to what I see as a legitimate use of such expressions. K. E. Logstrup writes in his work on theological ethics: Trust, in an elementary sense, belongs to every exchange of words. [...][B]y addressing someone—no matter the weight of what is being said—one takes up a certain tone in which the speaker, as it were, goes outside himself so as now to exist in the relationship of the speech to the other. This is why the demand—tacitly—is to the effect that one be received oneself when one’s tone of voice is received. When someone fails or refuses to hear the tone it therefore means that the speaker himself is being ignored, insofar as what has exposed itself is the speaker himself. The fact that all speech takes place in the midst of such an elementary trust is shown by the fact that the most trivial of remarks will ring false if one does not believe it will be taken as it is meant.1

A 3-min all-out test to determine peak oxygen uptake and the maximal steady state

Abstract: Burnley, M., Doust, J., Vanhatalo, A., A 3-min all-out test to determine peak oxygen uptake and the maximal steady state, Medicine & Science in Sports & Exercise. 38(11):1995-2003, November 2006. RAE2008