Nucleosomes and Cisplatin

In order to form a covalent complex with DNA inside human cells, cisplatin has to overcome the protective environment of a nucleosome, where DNA is complexed with histone proteins. Todd and Lippard (2010) expand our understanding of this process by describing the structure of a nucleosome containing a Pt-DNA adduct, which has important implications for more effective chemotherapeutic drug development

A Geometric Model for Odd Differential K-theory

Odd $K$-theory has the interesting property that it admits an infinite number of inequivalent differential refinements. In this paper we provide a bundle theoretic model for odd differential $K$-theory using the caloron correspondence and prove that this refinement is unique up to a unique natural isomorphism. We characterise the odd Chern character and its transgression form in terms of a connection and Higgs field and discuss some applications. Our model can be seen as the odd counterpart to the Simons-Sullivan construction of even differential $K$-theory. We use this model to prove a conjecture of Tradler-Wilson-Zeinalian regarding a related differential extension of odd $K$-theoryComment: 36 page

The Anti-tumour Agent, Cisplatin, and its Clinically Ineffective Isomer, Transplatin, Produce Unique Gene Expression Profiles in Human Cells

Cisplatin is a DNA-damaging anti-cancer agent that is widely used to treat a range of tumour types. Despite its clinical success, cisplatin treatment is still associated with a number of dose-limiting toxic side effects. The purpose of this study was to clarify the molecular events that are important in the anti-tumour activity of cisplatin, using gene expression profiling techniques. Currently, our incomplete understanding of this drug’s mechanism of action hinders the development of more efficient and less harmful cisplatin-based chemotherapeutics. In this study the effect of cisplatin on gene expression in human foreskin fibroblasts has been investigated using human 19K oligonucleotide microarrays. In addition its clinically inactive isomer, transplatin, was also tested. Dualfluor microarray experiments comparing treated and untreated cells were performed in quadruplicate. Cisplatin treatment was shown to significantly up- or down-regulate a consistent subset of genes. Many of these genes responded similarly to treatment with transplatin, the therapeutically inactive isomer of cisplatin. However, a smaller proportion of these transcripts underwent differential expression changes in response to the two isomers. Some of these genes may constitute part of the DNA damage response induced by cisplatin that is critical for its anti-tumour activity. Ultimately, the identification of gene expression responses unique to clinically active compounds, like cisplatin, could thus greatly benefit the design and development of improved chemotherapeutics

Ion-Molecule Reactions in Unsaturated Hydrocarbons: Allene, Propyne, Diacetylene, and Vinylacetylene

Ion-molecule reactions in allene, propyne, diacetylene, and vinylacetylene (1-buten-3-yne) have been studied at near-thermal energies by the technique of ion cyclotron resonance mass spectrometry. Rate coefficients and branching ratios are reported for the reactions of C_3H^+_n (n = 1-4) with allene and propyne and for the reactions of C_4H^+_n (n = 0-5) with diacetylene and vinylacetylene. Branching ratios are also given for the reactions of C_4H^+_n, C_5H_n, and C_6H^+_n with propyne and for reactions of C_6H^+_n with diacetylene and vinylacetylene. More than 90% of the reactive channels lead to product ions having a larger carbon skeleton than the reactant ion. Evidence for ions with the same m/e ratio having differing reactivities was obtained for C_3H^+_3, C_6H^+_7, and C_7H^+_7. Ion reaction sequences in allene and propyne were followed at higher pressures (l0^(-4) torr) to investigate secondary, tertiary, and higher order processes

Universal deformation formulas and breaking symmetry

AbstractWe show that an algebra with a non-nilpotent Lie group of automorphisms or “symmetries” (e.g., smooth functions on a manifold with such a group of diffeomorphisms) may generally be deformed (in the function case, “quantized”) in such a way that only a proper subgroup of the original group acts. This symmetry breaking is a consequence of the existence of certain “universal deformation formulas” which are elements, independent of the original algebra, in the tensor algebra of the enveloping algebra of the Lie algebra of the group

Biomolecular resource utilization in elementary cell-free gene circuits

We present a detailed dynamical model of the behavior of transcription-translation circuits in vitro that makes explicit the roles played by essential molecular resources. A set of simple two-gene test circuits operating in a cell-free biochemical 'breadboard' validate this model and highlight the consequences of limited resource availability. In particular, we are able to confirm the existence of biomolecular 'crosstalk' and isolate its individual sources. The implications of crosstalk for biomolecular circuit design and function are discussed