The triazine derivative 12459 is a potent G-quadruplex interacting agent that inhibits telomerase activity. This agent induces time- and dose-dependent telomere shortening, senescence-like growth arrest and apoptosis in the human A549 tumour cell line. We show here that 12459 induces a delayed apoptosis that activates the mitochondrial pathway. A549 cell lines selected for resistance to 12459 a...

Various helicases and single-stranded DNA (ssDNA) binding proteins are known to destabilize G-quadruplex (GQ) structures, which otherwise result in genomic instability. Bulk biochemical studies have shown that Bloom helicase (BLM) unfolds both intermolecular and intramolecular GQ in the presence of ATP. Using single molecule FRET, we show that binding of RecQ-core of BLM (will be referred to as...

This paper proposes a simple general equilibrium model of depression due to a financial shock and subsequent corporate-debt overhang. The " debt overhang problem " in the literature is the inefficiency caused by the penalty to the defaulters, such as the deterrence of new investments or the bankruptcy of debtors. This type of inefficiency is temporary and disappears as the new entrepreneurs ent...

Human telomeres possess a single-stranded DNA (ssDNA) overhang of TTAGGG repeats, which can self-fold into a G-quadruplex structure. POT1 binds specifically to the telomeric overhang and partners with TPP1 to regulate telomere lengthening and capping, although the mechanism remains elusive. Here, we show that POT1 binds stably to folded telomeric G-quadruplex DNA in a sequential manner, one oli...

OBJECTIVES There remains a lack of data on the reliability of methods to estimate tibial coverage achieved during total knee replacement. In order to address this gap, the intra- and interobserver reliability of a three-dimensional (3D) digital templating method was assessed with one symmetric and one asymmetric prosthesis design. METHODS A total of 120 template procedures were performed acco...

This paper studies the optimal contracting problem in a general cashow setup, and offers a framework to quantitatively assess the impact of agency problems. A closed form solution is obtained in the square-root mean-reverting cash ow process. In the geometric Brownian cashow setup, we embed the agency problem into Leland (1994), and nd that the debt-overhang problem lowers the optimal leverage....

There are two basic mechanisms that are associated with the maintenance of the telomere length, which endows cancer cells with unlimited proliferative potential. One mechanism, referred to as alternative lengthening of telomeres (ALT), accounts for approximately 10-15% of all human cancers. Tumours engaged in the ALT pathway are characterised by the presence of the single stranded 5'-C-rich tel...

Normal human cells cease proliferation after a finite number of population doublings, a phenomenon termed replicative senescence. This process, first convincingly described by Hayflick and Moorhead [Hayflick, L. & Moorhead, P. S. (1961) Exp. Cell Res. 25, 595-621] for cultured human fibroblasts 40 years ago, is suggested to be a fundamental defense against cancer. Several events have been demon...