Repair of mitomycin C mono- and interstrand cross-linked DNA adducts by UvrABC: a new model

Mitomycin C induces both MC-mono-dG and cross-linked dG-adducts in vivo. Interstrand cross-linked (ICL) dG-MC-dG-DNA adducts can prevent strand separation. In Escherichia coli cells, UvrABC repairs ICL lesions that cause DNA bending. The mechanisms and consequences of NER of ICL dG-MC-dG lesions that do not induce DNA bending remain unclear. Using DNA fragments containing a MC-mono-dG or an ICL dG-MC-dG adduct, we found (i) UvrABC incises only at the strand containing MC-mono-dG adducts; (ii) UvrABC makes three types of incisions on an ICL dG-MC-dG adduct: type 1, a single 5′ incision on 1 strand and a 3′ incision on the other; type 2, dual incisions on 1 strand and a single incision on the other; and type 3, dual incisions on both strands; and (iii) the cutting kinetics of type 3 is significantly faster than type 1 and type 2, and all of 3 types of cutting result in producing DSB. We found that UvrA, UvrA + UvrB and UvrA + UvrB + UvrC bind to MC-modified DNA specifically, and we did not detect any UvrB- and UvrB + UvrC–DNA complexes. Our findings challenge the current UvrABC incision model. We propose that DSBs resulted from NER of ICL dG-MC-dG adducts contribute to MC antitumor activity and mutations

The USTC co-opts an ancient machinery to drive piRNA transcription in C. elegans.

Piwi-interacting RNAs (piRNAs) engage Piwi proteins to suppress transposons and nonself nucleic acids and maintain genome integrity and are essential for fertility in a variety of organisms. In Caenorhabditis elegans, most piRNA precursors are transcribed from two genomic clusters that contain thousands of individual piRNA transcription units. While a few genes have been shown to be required for piRNA biogenesis, the mechanism of piRNA transcription remains elusive. Here we used functional proteomics approaches to identify an upstream sequence transcription complex (USTC) that is essential for piRNA biogenesis. The USTC contains piRNA silencing-defective 1 (PRDE-1), SNPC-4, twenty-one-U fouled-up 4 (TOFU-4), and TOFU-5. The USTC forms unique piRNA foci in germline nuclei and coats the piRNA cluster genomic loci. USTC factors associate with the Ruby motif just upstream of type I piRNA genes. USTC factors are also mutually dependent for binding to the piRNA clusters and forming the piRNA foci. Interestingly, USTC components bind differentially to piRNAs in the clusters and other noncoding RNA genes. These results reveal the USTC as a striking example of the repurposing of a general transcription factor complex to aid in genome defense against transposons

miRTarBase update 2014: an information resource for experimentally validated miRNA-target interactions

MicroRNAs (miRNAs) are small non-coding RNA molecules capable of negatively regulating gene expression to control many cellular mechanisms. The miRTarBase database (http://mirtarbase.mbc.nctu.edu.tw/) provides the most current and comprehensive information of experimentally validated miRNA-target interactions. The database was launched in 2010 with data sources for >100 published studies in the identification of miRNA targets, molecular networks of miRNA targets and systems biology, and the current release (2013, version 4) includes significant expansions and enhancements over the initial release (2010, version 1). This article reports the current status of and recent improvements to the database, including (i) a 14-fold increase to miRNA-target interaction entries, (ii) a miRNA-target network, (iii) expression profile of miRNA and its target gene, (iv) miRNA target-associated diseases and (v) additional utilities including an upgrade reminder and an error reporting/user feedback system

Self-assembly of porous copper oxide hierarchical nanostructures for selective determinations of glucose and ascorbic acid

The simple design of CuO micro-/nanostructures has recently attracted tremendous interest particularly for the enzyme-less sensing of biological molecules due to their intrinsic electronic and catalytic properties. Consequently attention has been directed to the development of new CuO nanomaterials that have multi-interdisciplinary applications. Herein, we report for the first time the fabrication of hierarchical porous CuO micro-/nanostructures with flower- and hollow sphere-like morphology via a facile hydrothermal method. Our experimental findings clarify that the source of the copper-ions effectively control the assembly of CuO nano-building blocks via the one-step hydrolysis of [Cu(NH3)4(H2O)2]SO4 and [Cu(NH3)4(H2O)2]Cl2 precursors, which produce hollow sphere and flower-like morphologies for sensitive and selective determination of ascorbic acid and glucose, respectively. Moreover, such unique properties of macro-/mesoporous CuO with defined dimensions and topologies offer minimized diffusive resistance for the dispersion of active sites. The best performance of the glucose and ascorbic sensor can be obtained at +0.55 V in 0.1 M sodium hydroxide solution. The as-prepared CuO modified (drop-casted) screen-printed electrodes (SPE) exhibit a fast electroactive response with high sensitivity within a wide concentration range of glucose and ascorbic acid in real samples. Significantly, the anion-dependent approach might be used to control effectively the expansion and features of other metal oxide micro-/nanostructures

Dimeric 1,3-propanediaminetetraacetato lanthanides as the precursors of catalysts for the oxidative coupling of methane

National Science Foundation of China [21133007, 21033006, 21373169]; Ministry of Science and Technology of China [2010CB732303, 2012CB214900]; PCSIRT [IRT1036]From neutral solutions, dimeric 1,3-propanediaminetetraacetato lanthanides (NH4)(2)[Ln(2)(1,3-pdta)(2)-(H2O)(4)]center dot 8H(2)O [Ln = La, 1; Ce, 2] and K-2[Ln(2)(1,3-pdta) 2(H2O)(4)]center dot 11H(2)O [Ln = La, 3; Ce, 4] (1,3-H(4)pdta = 1,3-propanediaminetetraacetic acid, C11H18N2O8) were isolated in high yields. The reaction of excess strontium nitrate with 1 resulted in the formation of a two dimensional coordination polymer [La-2(1,3pdta)(2)(H2O) 4](n)center dot[Sr-2(H2O) 6](n)center dot [La-2(1,3-pdta)(2)(H2O)(2)](n)center dot 18nH(2)O (5) at 70 degrees C. Complexes 1-4 show a similar central molecular structure. The lanthanide ions are coordinated by two nitrogen atoms, four carboxy oxygen atoms from one 1,3-pdta ligand, two from the neighboring 1,3-pdta ligand forming a fourmembered ring and two water molecules. Complex 5 has two kinds of dimeric lanthanum unit and extends into a 2D coordination polymer through strontium ions and bridged oxygen atoms, and forms a fourteen membered ring linked by oxygen atoms from carboxy groups of pdta. Complexes 1-4 are soluble in water. The C-13{1H} NMR experiments for complex 1 were tested in solution. Thermal products from 1 and 5 show good catalytic activities towards the oxidative coupling reaction of methane (OCM). The conversion of methane and selectivity to C-2 reached 29.7% and 51.7% at 750 degrees C for the product of 5. From TGA, XRD and SEM analyses, the thermal products from 1 and 5 are rod-and poly-shaped, which are assigned as lanthanum oxocarbonate and a mixture of La2O3, SrCO3 and La2O2CO3 for 1 and 5, respectively. The precursor method is favorable for the formation of regular shaped mixed oxides

Repair of mitomycin C mono- and interstrand cross-linked DNA adducts by UvrABC: a new model

Mitomycin C induces both MC-mono-dG and cross-linked dG-adducts in vivo. Interstrand cross-linked (ICL) dG-MC-dG-DNA adducts can prevent strand separation. In Escherichia coli cells, UvrABC repairs ICL lesions that cause DNA bending. The mechanisms and consequences of NER of ICL dG-MC-dG lesions that do not induce DNA bending remain unclear. Using DNA fragments containing a MC-mono-dG or an ICL dG-MC-dG adduct, we found (i) UvrABC incises only at the strand containing MC-mono-dG adducts; (ii) UvrABC makes three types of incisions on an ICL dG-MC-dG adduct: type 1, a single 5′ incision on 1 strand and a 3′ incision on the other; type 2, dual incisions on 1 strand and a single incision on the other; and type 3, dual incisions on both strands; and (iii) the cutting kinetics of type 3 is significantly faster than type 1 and type 2, and all of 3 types of cutting result in producing DSB. We found that UvrA, UvrA + UvrB and UvrA + UvrB + UvrC bind to MC-modified DNA specifically, and we did not detect any UvrB- and UvrB + UvrC–DNA complexes. Our findings challenge the current UvrABC incision model. We propose that DSBs resulted from NER of ICL dG-MC-dG adducts contribute to MC antitumor activity and mutations

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns