In situ identification of Gram-negative bacteria in human lungs using a topical fluorescent peptide targeting lipid A.

Respiratory infections in mechanically ventilated patients caused by Gram-negative bacteria are a major cause of morbidity. Rapid and unequivocal determination of the presence, localization, and abundance of bacteria is critical for positive resolution of the infections and could be used for patient stratification and for monitoring treatment efficacy. Here, we developed an in situ approach to visualize Gram-negative bacterial species and cellular infiltrates in distal human lungs in real time.

Magnetically activated adhesives: towards on-demand magnetic triggering of selected polymerisation reactions.

On-demand initiation of chemical reactions is becoming increasingly popular in many areas. The use of a magnetic field to trigger reactions is an intriguing concept, with vast potential in both research and industrial settings, though it remains a challenge as yet unsolved. Here we report the first example of on-demand magnetic activation of a polymerisation process using an anaerobic adhesive formulation as an example of this new approach toward triggering polymerisation reactions using an external magnetic field.

A Randomized Controlled Trial of Atorvastatin in Patients With Bronchiectasis Infected With Pseudomonas Aeruginosa: A Proof of Concept Study.

Background: There are no randomized controlled trials of statin therapy in patients with severe bronchiectasis who are chronically infected with Pseudomonas aeruginosa.

Methods: Thirty-two patients chronically infected with P aeruginosa were recruited in this double-blind cross-over randomized controlled trial. Sixteen patients were recruited in each arm, were given atorvastatin 80 mg or placebo for 3 months followed by a washout period for 6 weeks, and then crossed over and administered the alternative therapy for 3 months.

Molecular Recognition of Biomolecules by Chiral CdSe Quantum Dots.

Molecular recognition is one of the most important phenomena in Chemistry and Biology. Here we present a new way of enantiomeric molecular recognition using intrinsically chiral semiconductor nanocrystals as assays. Real-time confocal microscopy studies supported by circular dichroism spectroscopy data and theoretical modelling indicate an ability of left-handed molecules of cysteine and, to a smaller extent, histidine and arginine to discriminate between surfaces of left- and right-handed nanocrystals.

The chiral nano-world: chiroptically active quantum nanostructures.

Chirality is one of the key factors in molecular recognition, therefore the development of new chiral nanoparticles is of great interest to many fields of scientific endeavour including chemistry, biochemistry, pharmacology and medicine. Knowledge of the fundamental concepts relevant to chirality in nanosystems is also very important for further advancement of nanoscience and nanotechnology in general. Over the past years, the use of stereospecific chiral stabilising molecules has opened a new avenue to the area of nanocrystal research.

Lung Microbiota Changes Associated with Chronic Pseudomonas aeruginosa Lung Infection and the Impact of Intravenous Colistimethate Sodium.

Background: Exacerbations associated with chronic lung infection with Pseudomonas aeruginosa are a major contributor to morbidity, mortality and premature death in cystic fibrosis. Such exacerbations are treated with antibiotics, which generally lead to an improvement in lung function and reduced sputum P. aeruginosa density.

Optically Triggered Immune Response through Photocaged Oligonucleotides.

Bacterial and viral CpG oligonculeotides are unmethylated cytosine-phosphate-guanosine dinucleotide sequences and trigger an innate immune response through activation of the toll-like receptor 9 (TLR9). We have developed synthetic photocaged CpGs via site-specific incorporation of nitropiperonyloxymethyl (NPOM)-caged thymidine residues. These oligonucleotides enable the optical control of TLR9 function and thereby provide light-activation of an immune response.

Nuclear PTEN tumor-suppressor functions through maintaining heterochromatin structure.

The tumor suppressor, PTEN, is one of the most commonly mutated genes in cancer. Recently, PTEN has been shown to localize in the nucleus and is required to maintain genomic stability. Here, we show that nuclear PTEN, independent of its phosphatase activity, is essential for maintaining heterochromatin structure.

Intrinsic Chirality of CdSe/ZnS Quantum Dots and Quantum Rods.

A new class of chiral nanoparticles is of great interest not only for nanotechnology, but also for many other fields of scientific endeavor. Normally the chirality in semiconductor nanocrystals is induced by the initial presence of chiral ligands/stabilizer molecules. Here we report intrinsic chirality of ZnS coated CdSe quantum dots (QDs) and quantum rods (QRs) stabilized by achiral ligands.

Preparation of chiral quantum dots.

Chiral quantum dots (QDs) are expected to have a range of potential applications in photocatalysis, as specific antibacterial and cytotoxic drug-delivery agents, in assays, as sensors in asymmetric synthesis and enantioseparation, and as fluorescent chiral nanoprobes in biomedical and analytical technologies. In this protocol, we present procedures for the synthesis of chiral optically active QD nanostructures and their quality control using spectroscopic studies and transmission electron microscopy imaging. We closely examine various synthetic routes for the preparation of chiral CdS, CdSe, CdTe and doped ZnS QDs, as well as of chiral CdS nanotetrapods.

Garlic revisited: antimicrobial activity of allicin-containing garlic extracts against Burkholderia cepacia complex.

The antimicrobial activities of garlic and other plant alliums are primarily based on allicin, a thiosulphinate present in crushed garlic bulbs. We set out to determine if pure allicin and aqueous garlic extracts (AGE) exhibit antimicrobial properties against the Burkholderia cepacia complex (Bcc), the major bacterial phytopathogen for alliums and an intrinsically multiresistant and life-threatening human pathogen. We prepared an AGE from commercial garlic bulbs and used HPLC to quantify the amount of allicin therein using an aqueous allicin standard (AAS).

Cathelicidin host defence peptide augments clearance of pulmonary Pseudomonas aeruginosa infection by its influence on neutrophil function in vivo.

Cathelicidins are multifunctional cationic host-defence peptides (CHDP; also known as antimicrobial peptides) and an important component of innate host defence against infection. In addition to microbicidal potential, these peptides have properties with the capacity to modulate inflammation and immunity. However, the extent to which such properties play a significant role during infection in vivo has remained unclear.

Site-specific promoter caging enables optochemical gene activation in cells and animals.

In cell and molecular biology, double-stranded circular DNA constructs, known as plasmids, are extensively used to express a gene of interest. These gene expression systems rely on a specific promoter region to drive the transcription of genes either constitutively (i.e.

Synthesis Characterization and Photocatalytic Studies of Cobalt Ferrite-Silica-Titania Nanocomposites.

In this work, CoFe₂O₄@SiO₂@TiO₂ core-shell magnetic nanostructures have been prepared by coating of cobalt ferrite nanoparticles with the double SiO₂/TiO₂ layer using metallorganic precursors. The Transmission Electron Microscopy (TEM), Energy Dispersive X-Ray Analysis (EDX), Vibrational Sample Magnetometer (VSM) measurements and Raman spectroscopy results confirm the presence both of the silica and very thin TiO₂ layers. The core-shell nanoparticles have been sintered at 600 °C and used as a catalyst in photo-oxidation reactions of methylene blue under UV light.

Atorvastatin as a stable treatment in bronchiectasis: a randomised controlled trial.

Background: Bronchiectasis is characterised by chronic cough, sputum production, and recurrent chest infections. Pathogenesis is poorly understood, but excess neutrophilic airway inflammation is seen. Accumulating evidence suggests that statins have pleiotropic effects; therefore, these drugs could be a potential anti-inflammatory treatment for patients with bronchiectasis.

Recent Advances in the Application of Magnetic Nanoparticles as a Support for Homogeneous Catalysts.

Magnetic nanoparticles are a highly valuable substrate for the attachment of homogeneous inorganic and organic containing catalysts. This review deals with the very recent main advances in the development of various nanocatalytic systems by the immobilisation of homogeneous catalysts onto magnetic nanoparticles. We discuss magnetic core shell nanostructures (e.

Mannose-binding lectin deficiency and disease severity in non-cystic fibrosis bronchiectasis: a prospective study.

Background: Mannose-binding lectin (MBL) is a key component of innate immunity. MBL deficiency is common (10-30% of the general population depending on the definition used) and has been associated with disease progression in cystic fibrosis. We aimed to assess the effect of MBL deficiency on disease severity in non-cystic fibrosis bronchiectasis.

Draft Genome Sequence of a Stable Mucoid Strain of Pseudomonas aeruginosa PAO581 with a mucA25 Mutation.

A mutation in the mucA gene, which encodes a negative regulator of alginate production in Pseudomonas aeruginosa, is the main mechanism underlying the conversion to mucoidy in clinical isolates from patients with cystic fibrosis (CF). Here, we announce the draft genome sequence of the stable alginate-overproducing mucoid strain P. aeruginosa PAO581 with a mucA25 mutation, a derivative from the nonmucoid strains P.

Optochemical control of RNA interference in mammalian cells.

Short interfering RNAs (siRNAs) and microRNAs (miRNAs) have been widely used in mammalian tissue culture and model organisms to selectively silence genes of interest. One limitation of this technology is the lack of precise external control over the gene-silencing event. The use of photocleavable protecting groups installed on nucleobases is a promising strategy to circumvent this limitation, providing high spatial and temporal control over siRNA or miRNA activation.

Cellular delivery and photochemical activation of antisense agents through a nucleobase caging strategy.

Antisense oligonucleotides are powerful tools to regulate gene expression in cells and model organisms. However, a transfection or microinjection is typically needed for efficient delivery of the antisense agent. We report the conjugation of multiple HIV TAT peptides to a hairpin-protected antisense agent through a light-cleavable nucleobase caging group.

A lung segmental model of chronic Pseudomonas infection in sheep.

Background: Chronic lung infection with Pseudomonas aeruginosa is a major contributor to morbidity, mortality and premature death in cystic fibrosis. A new paradigm for managing such infections is needed, as are relevant and translatable animal models to identify and test concepts. We sought to improve on limitations associated with existing models of infection in small animals through developing a lung segmental model of chronic Pseudomonas infection in sheep.

Phase II studies of nebulised Arikace in CF patients with Pseudomonas aeruginosa infection.

Rationale: Arikace is a liposomal amikacin preparation for aerosol delivery with potent Pseudomonas aeruginosa killing and prolonged lung deposition.

Objectives: To examine the safety and efficacy of 28 days of once-daily Arikace in cystic fibrosis (CF) patients chronically infected with P aeruginosa.

Methods: 105 subjects were evaluated in double-blind, placebo-controlled studies.

Recovery of human DNA profiles from poached deer remains part 2: improved recovery protocol without the need for LCN analysis.

Although poaching is a common wildlife crime, the high and prohibitive cost of specialised animal testing means that many cases are left un-investigated. We previously described a novel approach to wildlife crime investigation that looked at the identification of human DNA on poached animal remains (Tobe, Govan and Welch, 2011). Human DNA was successfully isolated and amplified from simulated poaching incidents, however a low template protocol was required which made this method unsuitable for use in many laboratories.

Vitamin-D deficiency is associated with chronic bacterial colonisation and disease severity in bronchiectasis.

Introduction: Vitamin-D deficiency has been linked to an increased risk of respiratory infections. The objective of this study was to determine the frequency and clinical importance of vitamin-D deficiency in patients with bronchiectasis.

Methods: 25-hydroxyvitamin-D was measured by immunoassay in 402 stable patients with bronchiectasis.