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Coagulation is a critical component in the progression of liver disease. Identification of key molecules involved in the intrahepatic activation of coagulation (IAOC) will be instrumental in the development of effective therapies against liver disease. Using a mouse model of concanavalin A (Con A)-induced hepatitis, in which IAOC plays an essential role in causing liver injury, we uncovered a previously unknown procoagulant function of chitinase 3 like 1 (Chi3l1). Chi3l1 expression is dramatically elevated after Con A challenge, which is dependent on Con A-induced T cell activation, and the resulting IFN-γ and TNF-α productions. Compared to wild type mice, Chi3l1−/− mice show less IAOC, reduced tissue factor (TF) expression and attenuated liver injury. Reconstituting Chi3l1−/− mice with recombinant TF triggers IAOC and augments liver injury. Conclusion: Our data demonstrate that Chi3l1, through induction of TF via MAPK activation, promotes IAOC and tissue injury.

Application of a voltage ramp can result in denaturation of dsDNA and strand separation. We show that the potential at which half of the surface immobilised duplexes denature (the melting potential, E(m)) directly correlates with the calculated nearest neighbour and experimental melting temperatures; T(m), for a duplex is solution. The results demonstrate that the electrochemical melting potential measures the stability of the dsDNA, and therefore existing nearest neighbour melting models can be utilized to design DNA probes with predictable electrochemical melting potentials for future assay applications.

X-pyrene is a new nucleic acid duplex stabilizing cytosine analogue that combines enhanced π-stacking, hydrogen bonding and electrostatic interactions to greatly increase the stability of bulged DNA duplexes and DNA/RNA hybrids. X-pyrene is highly selective for guanine as a partner and duplex stability is reduced dramatically when X-pyrene or a neighboring base is mismatched. An NMR study indicates that the pyrene moiety stacks within the helix, and large changes in fluorescence emission on duplex formation are consistent with this. These favorable properties make X-pyrene a promising cytosine analogue for use in a variety of biological applications.

A triazole mimic of a DNA phosphodiester linkage has been produced by templated chemical ligation of oligonucleotides functionalized with 5′-azide and 3′-alkyne. The individual azide and alkyne oligonucleotides were synthesized by standard phosphoramidite methods and assembled using a straightforward ligation procedure. This highly efficient chemical equivalent of enzymatic DNA ligation has been used to assemble a 300-mer from three 100-mer oligonucleotides, demonstrating the total chemical synthesis of very long oligonucleotides. The base sequences of the DNA strands containing this artificial linkage were copied during PCR with high fidelity and a gene containing the triazole linker was functional in Escherichia coli .