RNA and DNA complexes with hemin [Fe(III) heme] are efficient peroxidases and peroxygenases: how do they do it and what does it mean?

Guanine-rich RNAs and DNAs from chromosomal telomeres and elsewhere that fold into guanine quadruplexes (G-quadruplexes), are found to complex tightly with porphyrins such as N-methylmesoporphyrin IX (NMM) and hemin [Fe(III) heme]. By themselves, these DNAs and RNAs are found to be efficient catalysts for porphyrin metallation. When complexed with hemin, under physiological conditions, these nucleic acids display robust peroxidase (one-electron oxidation), as well as peroxygenase (two-electron oxidation, or oxygen transfer) activity. These surprising catalytic properties, that frequently match the catalytic performance of natural peroxidase and P450 monooxygenase enzymes, have been the subject of significant mechanistic analysis, as well as having found utility in a wide range of biosensing and other applications. This review summarizes recent insights into a surprising yet fundamental property of many RNAs and DNAs, a property with undoubted ramifications for cellular oxidative disease, de novo hemoenzyme design, and our understanding of the evolution of early biocatalytic systems.

Tunable loading of single-stranded DNA on gold nanorods through the displacement of polyvinylpyrrolidone.

A quantitative and tunable loading of single-stranded (ss-DNA) molecules onto gold nanorods was achieved through a new method of surfactant exchange. This new method involves the exchange of cetyltrimethylammonium bromide surfactants for an intermediate stabilizing layer of polyvinylpyrrolidone and sodium dodecylsulfate. The intermediate layer of surfactants on the anisotropic gold particles was easily displaced by thiolated ss-DNA, forming a tunable density of single-stranded DNA molecules on the surfaces of the gold nanorods. The success of this ligand exchange process was monitored in part through the combination of extinction, X-ray photoelectron, and infrared absorption spectroscopies. The number of ss-DNA molecules per nanorod for nanorods with a high density of ss-DNA molecules was quantified through a combination of fluorescence measurements and elemental analysis, and the functionality of the nanorods capped with dense monolayers of DNA was assessed using a hybridization assay. Core-satellite assemblies were successfully prepared from spherical particles containing a probe DNA molecule and a nanorod core capped with complementary ss-DNA molecules. The methods demonstrated herein for quantitatively fine tuning and maximizing, or otherwise optimizing, the loading of ss-DNA in monolayers on gold nanorods could be a useful methodology for decorating gold nanoparticles with multiple types of biofunctional molecules.

Guanine-rich RNAs and DNAs that bind heme robustly catalyze oxygen transfer reactions.

Diverse guanine-rich RNAs and DNAs that fold to form guanine quadruplexes are known to form tight complexes with Fe(III) heme. We show here that a wide variety of such complexes robustly catalyze two-electron oxidations, transferring oxygen from hydrogen peroxide to thioanisole, indole, and styrene substrates. Use of (18)O-labeled hydrogen peroxide reveals the source of the oxygen transferred to form thioanisole sulfoxide and styrene oxide to be the activated ferryl moiety within these systems. Hammett analysis of the kinetics of thioanisole sulfoxide formation is unable to distinguish between a one-step, direct oxygen transfer and a two-step, oxygen rebound mechanism for this catalysis. Oxygen transfer to indole produces a range of products, including indigo and related dyes. Docking of heme onto a high-resolution structure of the G-quadruplex fold of Bcl-2 promoter DNA, which both binds heme and transfers oxygen, suggests a relatively open active site for this class of ribozymes and deoxyribozymes. That heme-dependent catalysis of oxygen transfer is a property of many RNAs and DNAs has ramifications for primordial evolution, enzyme design, cellular oxidative disease, and anticancer therapeutics.

Emergence and spread of vancomycin resistance among enterococci in Europe.

Nowadays, six types of acquired vancomycin resistance in enterococci are known; however, only VanA and to a lesser extent VanB are widely prevalent. Various genes encode acquired vancomycin resistance and these are typically associated with mobile genetic elements which allow resistance to spread clonally and laterally. The major reservoir of acquired vancomycin resistance is Enterococcus faecium; vancomycin-resistant Enterococcus faecalis are still rare. Population analysis of E. faecium has revealed a distinct subpopulation of hospital-acquired strain types, which can be differentiated by molecular typing methods (MLVA, MLST) from human commensal and animal strains. Hospital-acquired E. faecium have additional genomic content (accessory genome) including several factors known or supposed to be virulence-associated. Acquired ampicillin resistance is a major phenotypic marker of hospital-acquired E. faecium in Europe and experience has shown that it often precedes increasing rates of VRE with a delay of several years. Several factors are known to promote VRE colonisation and transmission; however, despite having populations with similar predispositions and preconditions, rates of VRE vary all over Europe.

Supplementary breast ultrasound screening in Asian women with negative but dense mammograms-a pilot study.

INTRODUCTION: Dense breasts are common in Asian women and they limit the sensitivity of mammography. This study evaluates the performance of supplementary breast ultrasound screening in Asian women with dense mammograms. MATERIALS AND METHODS: The study was approved by the hospital's Institutional Review Board. A prospective clinical trial was performed between September 2002 and November 2004. Asymptomatic Asian women with negative and dense mammograms were offered supplementary ultrasound screening for breast cancer. Ultrasound assessment was categorised as U1 to U4. U1 and U2 cases were recommended routine interval screening mammography. U3 cases were recommended follow-up ultrasound in 6 months and routine interval screening mammography and U4 cases were recommended biopsy. RESULTS: One hundred and forty-one women with mean age of 45.1 years were enrolled into the study. Mean scan time was 13.0 minutes (± 5.6 minutes) for bilateral vs 11.0 minutes (± 1.4 minutes) for unilateral scans. There were 10 patients and 14 patients in the in the U3 and U4 categories, respectively. Two U4 category patients were diagnosed with malignancy-a-6 mm ductal carcinoma-in-situ and a 13- mm invasive ductal carcinoma. The breast cancer detection rate was 1.4%. Sensitivity and specifi city were 100% (2/2) and 88.5% (92/104) respectively. The positive predictive value was 14.3% (2/14) and the negative predictive value was 100% (92/92). CONCLUSION: This pilot study reveals the usefulness of supplementary ultrasound screening in detecting early stage mammographically and clinically occult breast cancers in Asian women with dense breasts. A larger long-term study is, however, needed to assess its feasibility and impact on breast cancer prognosis.

Faecal carriage of extended-spectrum ß-lactamase-producing and AmpC ß-lactamase-producing bacteria among Danish army recruits.

During May and June 2008, 84 Danish army recruits were tested for faecal carriage of extended-spectrum ß-lactamase (ESBL)-producing and AmpC ß-lactamase-producing bacteria. Three ESBL-producing (CTX-M-14a) Escherichia coli isolates, two AmpC-producing (CMY-2) E. coli isolates and one AmpC-producing (CMY-34) Citrobacter freundii isolate were detected. Two of the CTX-M-14a E. coli isolates had similar pulsed-field gel electrophoresis and multilocus sequence typing profiles, indicating the same origin or transmission between the two army recruits. The bla(CTX-M-14a) genes were transferable to an E. coli recipient. These commensal bacteria therefore constitute a reservoir of resistance genes that can be transferred to other pathogenic bacteria in the intestine.