An in vitro screen of bacterial lipopolysaccharide biosynthetic enzymes identifies an inhibitor of ADP-heptose biosynthesis

The lipopolysaccharide (LPS)-rich outer membrane of gram-negative bacteria provides a protective barrier that insulates these organisms from the action of numerous antibiotics. Breach of the LPS layer can therefore provide access to the cell interior to otherwise impermeant toxic molecules and can expose vulnerable binding sites for immune system components such as complement. Inhibition of LPS biosynthesis, leading to a truncated LPS molecule, is an alternative strategy for antibacterial drug development in which this vital cellular structure is weakened. A significant challenge for in vitro screens of small molecules for inhibition of LPS biosynthesis is the difficulty in accessing the complex carbohydrate substrates. We have optimized an assay of the enzymes required for LPS heptose biosynthesis that simultaneously surveys five enzyme activities by using commercially available substrates and report its use in a small-molecule screen that identifies an inhibitor of heptose synthesis.

Quality of life in screen-detected and typical coeliac disease and the effect of excluding dietary gluten

It is widely recognized that 'asymptomatic' patients with coeliac disease often feel better after commencing a gluten-free diet. The aim of this study was to determine a measure of the quality of life in patients diagnosed as having coeliac disease detected both by screening and those with typical clinical symptoms.

Smokers:At risk for prostate cancer but unlikely to screen

Prostate cancer is the most commonly diagnosed cancer in men. Evidence suggests that smokers may be at increased risk of prostate cancer compared to non-smokers. In the present study we ask whether adult men who smoke are also less likely to undergo screening for prostate cancer. Adult men aged 46 and above completed a single questionnaire including demographic items and items concerning their smoking status and previous testing for prostate cancer. The questionnaire also included an 11 item numeracy scale. Compared to smokers, non-smokers and ex-smokers were around two times more likely to have undergone screening for prostate cancer, and had been tested more frequently. Smokers are not only more likely to develop prostate cancer, they are, paradoxically, less likely to undergo screening for prostate cancer. Health care professionals need to be cognizant of individual differences in screening behavior and that smokers have a reduced likelihood of choosing to screen. © 2012 Elsevier Ltd.

Comparison of frequency-selective screen-based linear to circular split-ring polarisation convertors

This study presents the use of periodic arrays of freestanding slot frequency-selective screens (FSS) as a means for generating circularly polarised signals from an incident linearly polarised signal at normal incidence to the structure. Measured and simulated results for crossed, linear and various ring slot element shapes in single and double-layer polarisation convertor structures are presented for 10 GHz operation. It is shown that 3 dB axial ratio (AR) bandwidths of 21% can be achieved with the one-layer perforated screen design and that the rate of change is lower than the double-layer structures. An insertion loss of 0.34 dB can be achieved for the split circular ring double-layer periodic array, and of the three topologies presented the hexagonal split-ring polarisation convertor gives the lowest variation of AR with angle of incidence 1.8 dB/45° and 3.6 dB/45° for the single and double-screen FSS, respectively. In addition, their tolerance to angle of incidence variation is presented. The capability of the surfaces reported here as twist polariser or spatial isolator components has been demonstrated with up to -30 dB isolation between incident and re-reflected signals for the double-layer designs being measured. © 2010 The Institution of Engineering and Technology.

RNAi screen identifies Jarid1b as a major regulator of mouse HSC activity

Histone methylation is a dynamic and reversible process proposed to directly impact on stem cell fate. The Jumonji (JmjC) domain-containing family of demethylases comprises 27 members which can demethylate mono-, di- and tri-methylated lysine residues of histone (or non-histone) targets. To evaluate their role in regulation of hematopoietic stem cell (HSC) behaviour we performed a RNAi-based screen and found that demethylases JARID1B (H3K4) and JHDM1F (H3K9) play opposing roles in regulation of HSC activity. Decrease in Jarid1b levels correlated with an in vitro expansion of HSC with preserved long term in vivo lympho-myeloid differentiation potential. Jarid1b knockdown was associated with an increase in expression levels of 5’ Hoxa cluster genes and CxCl5 , and reduced levels of Pu.1, Egr1 and Cav1. shRNA against Jhdmlf, in contrast, impaired hematopoietic reconstitution of bone marrow cells. Together, our studies identified Jarid1b as a negative, and Jhdmlf as a positive regulator of HSC activity.

One-step synthesis of ZnO nanosheets: a blue-white fluorophore

Zinc oxide is synthesised at low temperature (80A degrees C) in nanosheet geometry using a substrate-free, single-step, wet-chemical method and is found to act as a blue-white fluorophore. Investigation by atomic force microscopy, electron microscopy, and X-ray diffraction confirms zinc oxide material of nanosheet morphology where the individual nanosheets are polycrystalline in nature with the crystalline structure being of wurtzite character. Raman spectroscopy indicates the presence of various defects, while photoluminescence measurements show intense green (centre wavelength approximately 515 nm) blue (approximately 450 nm), and less dominant red (approximately 640 nm) emissions due to a variety of vacancy and interstitial defects, mostly associated with surfaces or grain boundaries. The resulting colour coordinate on the CIE-1931 standard is (0.23, 0.33), demonstrating potential for use as a blue-white fluorescent coating in conjunction with ultraviolet emitting LEDs. Although the defects are often treated as draw-backs of ZnO, here we demonstrate useful broadband visible fluorescence properties in as-prepared ZnO. 

In vivo safety of trypan blue use in vitreoretinal surgery

Purpose: The purpose of this study was to evaluate "in vivo" safety of trypan blue (TB) in patients undergoing TB-assisted internal limiting membrane or epiretinal membrane peeling. Methods: Prospective study including 21 patients (21 eyes) with full-thickness macular hole and/or epiretinal membrane undergoing TB-assisted internal limiting membrane/epiretinal membrane peeling. Main outcome measures included distance visual acuity, near visual acuity, amplitude of P50 and N95 of the pattern electroretinogram, and fundus autofluorescence; these were assessed preoperatively, at 6 months (n = 21) and 12 months (n = 10) postoperatively. Results: There was a statistically significant improvement in distance visual acuity, near visual acuity, P50, and N95 amplitude at 6 months and 12 months postoperatively. The mean logarithm of the minimum angle of resolution distance visual acuity and near visual acuity improved from baseline by 0.31 (SD 0.37) and 0.17 (SD 0.31) at 6 months, respectively, and by 0.4 (SD 0.25) and 0.35 (SD 0.28) at 12 months, respectively. The mean P50 and N95 component amplitudes improved by 28% compared with baseline at 6 months (P50 0.4 [SD 0.8]; N95 0.53 [SD 1.07]) and by 63% at 12 months (P50 0.9 [0.85]; N95 1.04 [1.34]). Autofluorescence did not demonstrate damage to the retinal pigment epithelium attributable to TB. Conclusion: No deleterious effects of TB were observed in this study. Copyright © 2011 Lippincott Williams &Wilkins.

Food of the Blue

An episode of BBC Radio 4's detective series 'Baldi'. Paolo Baldi finds himself in a world of superstar academics, but why are their bloodless corpses littering the college? And what is that thing they drink to rejuvenate the venerable institution?

Nile blue-based nano-sized pH sensors for simultaneous far-red and near-infrared live bioimaging

Diblock copolymer vesicles are tagged with pH-responsive Nile Blue-based labels and used as a new type of pH-responsive colorimetric/fluorescent biosensor for far-red and near-infrared imaging of live cells. The diblock copolymer vesicles described herein are based on poly(2-(methacryloyloxy)ethyl phosphorylcholine-block-2-(diisopropylamino)ethyl methacrylate) [PMPC-PDPA]: the biomimetic PMPC block is known to facilitate rapid cell uptake for a wide range of cell lines, while the PDPA block constitutes the pH-responsive component that enables facile vesicle self-assembly in aqueous solution. These biocompatible vesicles can be utilized to detect interstitial hypoxic/acidic regions in a tumor model via a pH-dependent colorimetric shift. In addition, they are also useful for selective intracellular staining of lysosomes and early endosomes via subtle changes in fluorescence emission. Such nanoparticles combine efficient cellular uptake with a pH-responsive Nile Blue dye label to produce a highly versatile dual capability probe. This is in marked contrast to small molecule dyes, which are usually poorly uptaken by cells, frequently exhibit cytotoxicity, and are characterized by intracellular distributions invariably dictated by their hydrophilic/hydrophobic balance.