Construction of heteroduplex DNA and in vitro model for functional analysis of mismatch repair

Functional deficiency of mismatch repair (MMR) system is one of the mechanisms of tumorigenesis. With the development of the investigation and the requirement from the clinical diagnosis and treatment it is necessary to build up a method to evaluate the functional status of the whole MMR system in the concerned tumors. The original ssDNA and dsDNA from wild type (wt) bacteriophage M13mp2 and its three derivates with mutation points in the     

Developing Reflective Practice in Information Systems Development: Further Progress on the Gestation of an Evaluative Framework

It is argued in this paper that evaluative activities in relation to systems development have traditionally focussed on the financial worth of the product. This approach has excluded the appraisal of important issues such as the process for building the product, the performance of the systems development team, the methods used and the organisational impact of the implemented System. In response to the traditional approach, which is skewed towards quantification techniques, a three stage framework is proposed. The three stages are iterative. The first being concerned with establishing an appropriate focus and resolution level for the evaluation, the second uses a control model to identify relevant outputs, appropriate sensors and comparators and performance criteria. The third is about selecting more sophisticated paradigms for assessing processes and their outputs. It is contended that although the specific focus of this paper is systems development, the framework could be used in any organisational context where products and services are developed and produced.     

Autoxidation of hermidin: an ESR study

Summary Aqueous solutions of hermidin readily give rise to a blue transient radical-anion on exposure to air, the identity of which has been established by ESR spectroscopy.Acknowledgment. I thank Professor R. H. Thomson for helpful discussion.     

Genomic alterations in cultured human embryonic stem cells

Cultured human embryonic stem cell (hESC) lines are an invaluable resource because they provide a uniform and stable genetic system for functional analyses and therapeutic applications. Nevertheless, these dividing cells, like other cells, probably undergo spontaneous mutation at a rate of 10(-9) per nucleotide. Because each mutant has only a few progeny, the overall biological properties of the cell culture are not altered unless a mutation provides a survival or growth advantage. Clonal evolution that leads to emergence of a dominant mutant genotype may potentially affect cellular phenotype as well. We assessed the genomic fidelity of paired early- and late-passage hESC lines in the course of tissue culture. Relative to early-passage lines, eight of nine late-passage hESC lines had one or more genomic alterations commonly observed in human cancers, including aberrations in copy number (45%), mitochondrial DNA sequence (22%) and gene promoter methylation (90%), although the latter was essentially restricted to 2 of 14 promoters examined. The observation that hESC lines maintained in vitro develop genetic and epigenetic alterations implies that periodic monitoring of these lines will be required before they are used in in vivo applications and that some late-passage hESC lines may be unusable for therapeutic purposes.     

Deposition of 1.88-billion-year-old iron formations as a consequence of rapid crustal growth

Iron formations are chemical sedimentary rocks comprising layers of iron-rich and silica-rich minerals whose deposition requires anoxic and iron-rich (ferruginous) sea water. Their demise after the rise in atmospheric oxygen by 2.32?billion years (Gyr) ago has been attributed to the removal of dissolved iron through progressive oxidation or sulphidation of the deep ocean. Therefore, a sudden return of voluminous iron formations nearly 500?million years later poses an apparent conundrum. Most late Palaeoproterozoic iron formations are about 1.88?Gyr old and occur in the Superior region of North America. Major iron formations are also preserved in Australia, but these were apparently deposited after the transition to a sulphidic ocean at 1.84?Gyr ago that should have terminated iron formation deposition, implying that they reflect local marine conditions. Here we date zircons in tuff layers to show that iron formations in the Frere Formation of Western Australia are about 1.88?Gyr old, indicating that the deposition of iron formations from two disparate cratons was coeval and probably reflects global ocean chemistry. The sudden reappearance of major iron formations at 1.88?Gyr ago--contemporaneous with peaks in global mafic-ultramafic magmatism, juvenile continental and oceanic crust formation, mantle depletion and volcanogenic massive sulphide formation--suggests deposition of iron formations as a consequence of major mantle activity and rapid crustal growth. Our findings support the idea that enhanced submarine volcanism and hydrothermal activity linked to a peak in mantle melting released large volumes of ferrous iron and other reductants that overwhelmed the sulphate and oxygen reservoirs of the ocean, decoupling atmospheric and seawater redox states, and causing the return of widespread ferruginous conditions. Iron formations formed on clastic-starved coastal shelves where dissolved iron upwelled and mixed with oxygenated surface water. The disappearance of iron formations after this event may reflect waning mafic-ultramafic magmatism and a diminished flux of hydrothermal iron relative to seawater oxidants.     

The structure of H5N1 avian influenza neuraminidase suggests new opportunities for drug design

The worldwide spread of H5N1 avian influenza has raised concerns that this virus might acquire the ability to pass readily among humans and cause a pandemic. Two anti-influenza drugs currently being used to treat infected patients are oseltamivir (Tamiflu) and zanamivir (Relenza), both of which target the neuraminidase enzyme of the virus. Reports of the emergence of drug resistance make the development of new anti-influenza molecules a priority. Neuraminidases from influenza type A viruses form two genetically distinct groups: group-1 contains the N1 neuraminidase of the H5N1 avian virus and group-2 contains the N2 and N9 enzymes used for the structure-based design of current drugs. Here we show by X-ray crystallography that these two groups are structurally distinct. Group-1 neuraminidases contain a cavity adjacent to their active sites that closes on ligand binding. Our analysis suggests that it may be possible to exploit the size and location of the group-1 cavity to develop new anti-influenza drugs.