DNA Intercalators Inhibit Eukaryotic Ribosomal RNA Synthesis by Impairing the Initiation of Transcription.

In eukaryotes, ribosome biogenesis is driven by the synthesis of the ribosomal RNA (rRNA) by RNA polymerase I (Pol-I) and is tightly linked to cell growth and proliferation. The 3D-structure of the rDNA promoter plays an important, yet not fully understood role in regulating rRNA synthesis. We hypothesized that DNA intercalators/groove binders could affect this structure and disrupt rRNA transcription.

Rapid quantification of microRNAs in plasma using a fast real-time PCR system.

The ability to rapidly detect circulating small RNAs, in particular microRNAs (miRNAs), would further increase their already established potential as biomarkers for a range of conditions. One rate-limiting factor in miRNA detection is the time taken to perform quantitative real-time PCR (qPCR) amplification. We therefore evaluated the ability of a novel thermal cycler to perform this step in less than 10 minutes.

Old drug, new target: ellipticines selectively inhibit RNA polymerase I transcription.

Transcription by RNA polymerase I (Pol-I) is the main driving force behind ribosome biogenesis, a fundamental cellular process that requires the coordinated transcription of all three nuclear polymerases. Increased Pol-I transcription and the concurrent increase in ribosome biogenesis has been linked to the high rates of proliferation in cancers. The ellipticine family contains a number of potent anticancer therapeutic agents, some having progressed to stage I and II clinical trials; however, the mechanism by which many of the compounds work remains unclear.

A calcium-dependent interaction between calmodulin and the calponin homology domain of human IQGAP1.

IQGAPs are cytoskeletal scaffolding proteins which collect information from a variety of signalling pathways and pass it on to the microfilaments and microtubules. There is a well-characterised interaction between IQGAP and calmodulin through a series of IQ-motifs towards the middle of the primary sequence. However, it has been shown previously that the calponin homology domain (CHD), located at the N-terminus of the protein, can also interact weakly with calmodulin.

A sulfone-based strategy for the preparation of 2,4-disubstituted furan derivatives.

2,4-Disubstituted furans are prepared by treating 2,3-dibromo-1-phenylsulfonyl-1-propene (DBP, 2) with 1,3-diketones under basic conditions. The furan-forming step involves a deacetylation, and the selectivity of this process depends upon the steric demand of the R group. The substituent in position 4 is elaborated by reaction of sulfonyl carbanions with alkyl halides, acyl halides, and aldehydes.

Stereoselective construction of cis-2,6-disubstituted tetrahydropyrans via an intramolecular bismuth-mediated oxa-conjugate addition reaction.

The intramolecular oxa-conjugate addition of tethered triethylsilyloxy substituted alpha,beta-unsaturated ketones mediated by bismuth(III) nitrate pentahydrate provides a mild and efficient method for the stereoselective construction of cis-2,6-disubstituted tetrahydropyrans.

Characteristics associated with neuropathy and/or retinopathy in a hospital outpatient diabetic clinic.

Background: The incidence of diabetes is increasing worldwide and with it the risk of diabetic complications. The aim of this study was to characterise parameters associated with neuropathy and/or retinopathy in a hospital outpatient diabetic clinic population.

Method: A structured questionnaire addressing diabetes related factors and demography was administered to a cross-sectional sample of patients (n = 290) with type 1 and type 2 diabetes attending a hospital diabetic outpatient clinic.

Aromatase inhibition by 15-deoxy-prostaglandin J(2) (15-dPGJ(2)) and N-(4-hydroxyphenyl)-retinamide (4HPR) is associated with enhanced ceramide production.

Inhibition of aromatase activity is an established endocrine therapy in the treatment of hormone-dependent breast cancer. Recent studies on aromatase inhibition by the synthetic retinoid 4HPR, also known as fenretinide, and the PPARgamma agonist 15-dPGJ(2) have implicated a direct receptor-independent, redox-sensitive mechanism of action. The signalling molecule ceramide has also been previously implicated as a negative regulator of aromatase activity.