Can ends justify the means?: Telomeres and the mechanisms of replicative senescence and immortalization in mammalian cells

Finite replicative lifespan, or senescence, of mammalian cells in culture is a phenomenon that has generated much curiosity since its description. The obvious significance of senescence to organismal aging and the development of cancer has engendered a long-lasting and lively debate about its mechanisms. Recent discoveries concerning the phenotypes of telomerase knockout mice, the consequences of telomerase reexpression in somatic cells, and genes that regulate senescence have provided striking molecular insights but also have uncovered important new questions. The objective of this review is to reconcile old observations with new molecular details and to focus attention on the key remaining puzzles.

Precise sequence complementarity between yeast chromosome ends and two classes of just-subtelomeric sequences

The terminal regions (last 20 kb) of Saccharomyces cerevisiae chromosomes universally contain blocks of precise sequence similarity to other chromosome terminal regions. The left and right terminal regions are distinct in the sense that the sequence similarities between them are reverse complements. Direct sequence similarity occurs between the left terminal regions and also between the right terminal regions, but not between any left ends and right ends. With minor exceptions the relationships range from 80% to 100% match within blocks. The regions of similarity are composites of familiar and unfamiliar repeated sequences as well as what could be considered “single-copy” (or better “two-copy”) sequences. All terminal regions were compared with all other chromosomes, forward and reverse complement, and 768 comparisons are diagrammed. It appears there has been an extensive history of sequence exchange or copying between terminal regions. The subtelomeric sequences fall into two classes. Seventeen of the chromosome ends terminate with the Y′ repeat, while 15 end with the 800-nt “X2” repeats just adjacent to the telomerase simple repeats. The just-subterminal repeats are very similar to each other except that chromosome 1 right end is more divergent.

Repair of x-ray-induced DNA double-strand breaks in specific Not I restriction fragments in human fibroblasts: joining of correct and incorrect ends.

An assay that allows measurement of absolute induction frequencies for DNA double-strand breaks (dsbs) in defined regions of the genome and that quantitates rejoining of correct DNA ends has been used to study repair of dsbs in normal human fibroblasts after x-irradiation. The approach involves hybridization of single-copy DNA probes to Not I restriction fragments separated according to size by pulsed-field gel electrophoresis. Induction of dsbs is quantitated from the decrease in the intensity of the hybridizing restriction fragment and an accumulation of a smear below the band. Rejoining of dsbs results in reconstitution of the intact restriction fragment only if correct DNA ends are joined. By comparing results from this technique with results from a conventional electrophoresis assay that detects all rejoining events, it is possible to quantitate the misrejoining frequency. Three Not I fragments on the long arm of chromosome 21 were investigated with regard to dsb induction, yielding an identical induction rate of 5.8 X 10(-3) break per megabase pair per Gy. Correct dsb rejoining was measured for two of these Not I fragments after initial doses of 80 and 160 Gy. The misrejoining frequency was about 25% for both fragments and was independent of dose. This result appears to be representative for the whole genome as shown by analysis of the entire Not I fragment distribution. The correct rejoining events primarily occurred within the first 2 h, while the misrejoining kinetics included a much slower component, with about half of the events occurring between 2 and 24 h. These misrejoining kinetics are similar to those previously reported for production of exchange aberrations in interphase chromosomes.

The concept of 'economic activity' in the EU treaty: from ideological dead-ends to workable judicial concepts. Research Paper in Law 06/2011

[From the Introduction]. The economic rules, or put more ambitiously, the economic constitution of the Treaty,1 only apply to economic activities. This general principle remains valid, even if some authors strive to demonstrate that certain Treaty rules also apply in the absence of an economic activity,2 and despite the fact that non-economic (horizontal) Treaty provisions (e.g. principle of nondiscrimination, rules on citizenship) are also applicable in the absence of any economic activity.3 Indeed, the exercise of some economic activity transcends the concepts of ‘goods’ (having positive or negative market value),4 workers (even if admitted in an extensive manner),5 and services (offered for remuneration).6 It is also economic activity or ‘the activity of offering goods and services into the market’7 that characterises an ‘undertaking’ thus making the competition rules applicable. Further, it is for regulating economic activity that Article 115 TFEU, Article 106(3) TFEU and most other legal bases in the TFEU provide harmonisation powers in favour of the EU. Last but not least, Article 14 TFEU on the distinction between services of general economic interest (SGEIs) and non-economic services of general interest (NESGIs), as well as Protocol n. 26 on Services of General Interest (SGIs) confirm the constitutional significance of the distinction between economic and non-economic: a means of dividing competences between the EU and the member states. The distinction between economic and non-economic activities is fraught with legal and technical intricacies – the latter being generated by dynamic technological advances and regulatory experimentation. More importantly, however, the distinction is overcharged with political and ideological significations and misunderstandings and, even, terminological confusions.8

This is photography, its means and ends,

Mode of access: Internet.

Study of the effects of turnout design on registration accuracy of propeller meters placed in downstream ends of turnout pipes /

Mode of access: Internet.

Dog Breaking : the most expeditious, certain and easy method, whether great excellence or only mediocrity be required, with odds and ends for those who love the dog and gun /

Mode of access: Internet.

Human odds and ends/

Mode of access: Internet.