MYC assembles and stimulates topoisomerases 1 and 2 in a “topoisome”

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Dependence Functions and Frailties

This note considers association between nonnegative random variables in which the two observed survival times depend on an unobservable random variable via the proportional hazard model. When the random variables are subject to censoring, the conditional hazard functions provides a reasonable means of describing the association between the two variables. A numerical example demonstrating association in disease incidence in ordered pairs of individuals is analysed. Also, examples of distributions satisfying the notions of dependence considered are provided.     

Topological stress is responsible for the detrimental outcomes of head-on replication-transcription conflicts

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Observation of positive selection within hypervariable regions of a newly identified DNA virus (SEN virus)

To elucidate the evolution of SEN virus (SEN-V), serial sequences of chronically SEN-V-infected patients were analyzed. In the hypervariable regions, non-synonymous substitutions significantly predominated. This could be attributed to positive selection in evading immune surveillance of the hosts and to establish a persistent infection. On the basis of the sequences in the two open reading frames of SEN-V DNA, the rate of synonymous substitutions was 7.32×10⁻⁴ per site per year. Since this rate is close to RNA viruses and higher than other DNA viruses, the SEN-V might be replicated by machinery with poor or no proofreading function.     

Accumulation of Species-Specific Amino Acid Replacements That Cause Loss of Particular Protein Functions in Buchnera, an Endocellular Bacterial Symbiont

Endosymbiotic bacteria live in animal cells and are transmitted vertically at the time of the host's reproduction. In view of their small and asexual populations with infrequent chances of recombination, these endocellular bacteria are expected to accumulate mildly deleterious mutations. Previous studies showed that the DNA sequences of these bacteria evolved faster than those of free-living bacteria. In this study, we compared all the ORFs of Buchnera, an endocellular bacterial symbiont of aphids, with those of 34 other prokaryotic organisms and estimated the effect of the accelerated evolution of Buchnera on the functions of its proteins. It was revealed that Buchnera proteins contain many mutations at the sites where sequences are conserved in their orthologues in many other organisms. In addition, amino acid replacements at the conserved sites are mostly changes to physicochemically different amino acids. These results suggest that functions and conformations of Buchnera proteins have been seriously impaired or strongly modified. Indeed, extensive loss of functional motifs was observed in some Buchnera proteins. In many Buchnera proteins mutations were not detected evenly throughout each molecule but tended to accumulate in some functional units, possibly leading to loss of specific functions. As Buchnera has an unusual and limited gene repertory, it is conceivable that the manner of interactions among its proteins has been changed, and thus, functional constraints over their amino acid residues have also been changed during evolution. This may account for the loss of some functional units only in the Buchnera proteins. We obtained evidence that amino acid replacements in Buchnera were not always deleterious, but neutral or, in some cases, even positively selected. Received: 14 December 2000 / Accepted: 12 March 2001     

Differential influence of DNA supercoiling on in vivo strength of promoters varying in structure and organisation in E. coli

DNA supercoiling is known to influence promoter activity in vitro and in vivo in a promoter-dependent manner in prokaryotes. In order to investigate how topology may influence promoter function, we have studied two kinds of promoter variants, (i) where only the spacer region is altered, and (ii) where the same promoter is tandemly repeated in either the same or opposite orientation. These promoters respond very differently to alterations in DNA supercoiling, suggesting that the overall structure of the promoter and its context contribute to the differential response to alterations in supercoiling in vivo.     

Test of Independence Against a Class of Ordered Alternatives in an R × C Contingency Table

Test procedures are developed for testing the hypotheses of independence in a two-way contingency table against a class of ordered alternatives defined in terms of pooled crossproduct ratios. The alternatives hypotheses of “positive dependence” defines new notions of dependence. The distribution of the test statistics is obtained. Admissibility of the test is deduced and power comparison with some known test procedures are given. A numerical example is presented to illustrate the techniques developed.