Extragingival pyogenic granuloma: a case report

The pyogenic granuloma is thought to represent an exuberant tissue response to local irritation or trauma

Single-atom imaging of fermions in a quantum-gas microscope

Single-atom-resolved detection in optical lattices using quantum-gas microscopes has enabled a new generation of experiments in the field of quantum simulation. Fluorescence imaging of individual atoms has so far been achieved for bosonic species with optical molasses cooling, whereas detection of fermionic alkaline atoms in optical lattices by this method has proven more challenging. Here we demonstrate single-site- and single-atom-resolved fluorescence imaging of fermionic potassium-40 atoms in a quantum-gas microscope setup using electromagnetically-induced-transparency cooling. We detected on average 1000 fluorescence photons from a single atom within 1.5s, while keeping it close to the vibrational ground state of the optical lattice. Our results will enable the study of strongly correlated fermionic quantum systems in optical lattices with resolution at the single-atom level, and give access to observables such as the local entropy distribution and individual defects in fermionic Mott insulators or anti-ferromagnetically ordered phases.Comment: 7 pages, 5 figures; Nature Physics, published online 13 July 201

Decoupling competing surface binding kinetics and reconfiguration of receptor footprint for ultrasensitive stress assays

Cantilever arrays have been used to monitor biochemical interactions and their associated stress. However, it is often necessary to passivate the underside of the cantilever to prevent unwanted ligand adsorption, and this process requires tedious optimization. Here, we show a way to immobilize membrane receptors on nanomechanical cantilevers so that they can function without passivating the underlying surface. Using equilibrium theory, we quantitatively describe the mechanical responses of vancomycin, human immunodeficiency virus type 1 antigens and coagulation factor VIII captured on the cantilever in the presence of competing stresses from the top and bottom cantilever surfaces. We show that the area per receptor molecule on the cantilever surface influences ligand-receptor binding and plays an important role on stress. Our results offer a new way to sense biomolecules and will aid in the creation of ultrasensitive biosensors

Surface mediated cooperative interactions of drugs enhance mechanical forces for antibiotic action

The alarming increase of pathogenic bacteria that are resistant to multiple antibiotics is now recognized as a major health issue fuelling demand for new drugs. Bacterial resistance is often caused by molecular changes at the bacterial surface, which alter the nature of specific drug-target interactions. Here, we identify a novel mechanism by which drug-target interactions in resistant bacteria can be enhanced. We examined the surface forces generated by four antibiotics; vancomycin, ristomycin, chloroeremomycin and oritavancin against drug-susceptible and drug-resistant targets on a cantilever and demonstrated significant differences in mechanical response when drug-resistant targets are challenged with different antibiotics although no significant differences were observed when using susceptible targets. Remarkably, the binding affinity for oritavancin against drug-resistant targets (70 nM) was found to be 11,000 times stronger than for vancomycin (800 μM), a powerful antibiotic used as the last resort treatment for streptococcal and staphylococcal bacteria including methicillin-resistant Staphylococcus aureus (MRSA). Using an exactly solvable model, which takes into account the solvent and membrane effects, we demonstrate that drug-target interactions are strengthened by pronounced polyvalent interactions catalyzed by the surface itself. These findings further enhance our understanding of antibiotic mode of action and will enable development of more effective therapies.We thank the EPSRC Interdisciplinary Research Centre in Nanotechnology (Cambridge, UCL, Bristol (GR/R45680/01), the EPSRC Grand Challenge in Nanotechnology for Healthcare (EP/G0620064/1), I-sense EPSRC IRC in Early Warning Sensing Systems for Infectious Diseases (EP/G062064/1), the EPSRC Speculative Engineering Program (EP/D50925/1), Royal Society (RS), Medicine Company Inc., USA, NHMRC Australia Fellowship (AF511105), UCL Graduate School Scholarship, UCL COMPLEX, Bio Nano Consulting (BNC), European Union FP7 Project VSMMART Nano (managed by BNC) and NHS Trusts Biomedical Research Centre (BRC) for funding

A randomised, controlled crossover comparison of the C-MAC videolaryngoscope with direct laryngoscopy in 150 patients during routine induction of anaesthesia

<p>Abstract</p> <p>Background</p> <p>The C-MAC^®(Karl Storz, Tuttlingen, Germany) has recently been introduced as a new device for videolaryngoscopy guided intubation. The purpose of the present study was to compare for the first time the C-MAC with conventional direct laryngoscopy in 150 patients during routine induction of anaesthesia.</p> <p>Methods</p> <p>After approval of the institutional review board and written informed consent, 150 patients (ASA I-III) with general anaesthesia were enrolled. Computer-based open crossover randomisation was used to determine the sequence of the three laryngoscopies: Conventional direct laryngoscopy (HEINE Macintosh classic, Herrsching, Germany; blade sizes 3 or 4; <it>DL </it>group), C-MAC size 3 (<it>C-MAC3 </it>group) and C-MAC size 4 (<it>C-MAC4 </it>group) videolaryngoscopy, respectively. After 50 patients, laryngoscopy technique in the C-MAC4 group was changed to the straight blade technique described by Miller (C-MAC4/SBT).</p> <p>Results</p> <p>Including all 150 patients (70 male, aged (median [range]) 53 [20-82] years, 80 [48-179] kg), there was no difference of glottic view between DL, C-MAC3, C-MAC4, and C-MAC4/SBT groups; however, worst glottic view (C/L 4) was only seen with DL, but not with C-MAC videolaryngoscopy. In the subgroup of patients that had suboptimal glottic view with DL (C/L≥2a; n = 24), glottic view was improved in the C-MAC4/SBT group; C/L class improved by three classes in 5 patients, by two classes in 2 patients, by one class in 8 patients, remained unchanged in 8 patients, or decreased by two classes in 1 patient. The median (range) time taken for tracheal intubation in the DL, C-MAC3, C-MAC4 and C-MAC4/SBT groups was 8 sec (2-91 sec; n = 44), 10 sec (2-60 sec; n = 37), 8 sec (5-80 sec; n = 18) and 12 sec (2-70 sec; n = 51), respectively.</p> <p>Conclusions</p> <p>Combining the benefits of conventional direct laryngoscopy and videolaryngoscopy in one device, the C-MAC may serve as a standard intubation device for both routine airway management and educational purposes. However, in patients with suboptimal glottic view (C/L≥2a), the C-MAC size 4 with straight blade technique may reduce the number of C/L 3 or C/L 4 views, and therefore facilitate intubation. Further studies on patients with difficult airway should be performed to confirm these findings.</p

Reconstruction and analysis of genome-scale metabolic model of a photosynthetic bacterium

<p>Abstract</p> <p>Background</p> <p><it>Synechocystis </it>sp. PCC6803 is a cyanobacterium considered as a candidate photo-biological production platform - an attractive cell factory capable of using CO₂and light as carbon and energy source, respectively. In order to enable efficient use of metabolic potential of <it>Synechocystis </it>sp. PCC6803, it is of importance to develop tools for uncovering stoichiometric and regulatory principles in the <it>Synechocystis </it>metabolic network.</p> <p>Results</p> <p>We report the most comprehensive metabolic model of <it>Synechocystis </it>sp. PCC6803 available, <it>i</it>Syn669, which includes 882 reactions, associated with 669 genes, and 790 metabolites. The model includes a detailed biomass equation which encompasses elementary building blocks that are needed for cell growth, as well as a detailed stoichiometric representation of photosynthesis. We demonstrate applicability of <it>i</it>Syn669 for stoichiometric analysis by simulating three physiologically relevant growth conditions of <it>Synechocystis </it>sp. PCC6803, and through <it>in silico </it>metabolic engineering simulations that allowed identification of a set of gene knock-out candidates towards enhanced succinate production. Gene essentiality and hydrogen production potential have also been assessed. Furthermore, <it>i</it>Syn669 was used as a transcriptomic data integration scaffold and thereby we found metabolic hot-spots around which gene regulation is dominant during light-shifting growth regimes.</p> <p>Conclusions</p> <p><it>i</it>Syn669 provides a platform for facilitating the development of cyanobacteria as microbial cell factories.</p

Research Article A New Informatics Framework for Evaluating the Codon Usage Metrics, Evolutionary Models and Phylogeographic Reconstruction of Tomato Yellow Leaf Curl Virus (TYLCV) in Different Regions of Asian Countries

Not AvailableTomato yellow leaf curl virus (TYLCV) is a major devastating viral disease, majorly affecting the tomato production globally. The disease is majorly transmitted by the Whitefly. The Begomovirus (TYLCV) having a six major protein coding genes, among them the C1/AC1 is evidently associated with viral replication. Owing to immense role of C1/AC1 gene, the present study is an initial effort to elucidate the factors shaping the codon usage bias and evolutionary pattern of TYLCV-C1/AC1 gene in five major Asian countries. Based on publicly available nucleotide sequence data the Codon usage pattern, Evolutionary and Phylogeographic reconstruction was carried out. The study revealed the presence of significant variation between the codon bias indices in all the selected regions. Implying that the codon usage pattern indices (eNC, CAI, RCDI, GRAVY, Aromo) are seriously affected by selection and mutational pressure, taking a supremacy in shaping the codon usage bias of viral gene. Further, the tMRCA age was 1853, 1939, 1855, 1944, 1828 for China, India, Iran, Oman and South Korea, respectively for TYLCV-C1/AC1 gene. The integrated analysis of Codon usage bias, Evolutionary rate and Phylogeography analysis in viruses signifies the positive role of selection and mutational pressure among the selected regions for TYLCV (C1/AC1) gene.Not Availabl

PECAM-Independent Thioglycollate Peritonitis Is Associated With a Locus on Murine Chromosome 2

Background: Previous studies have demonstrated that knockout or inhibition of Platelet/Endothelial Cell Adhesion Molecule (PECAM, CD31) in a number of murine strains results in impaired inflammatory responses, but that no such phenotype is seen in the C57BL/6 (B6) murine background. Methodology/Principal Findings: We have undertaken a quantitative trait locus (QTL) mapping effort between FVB/n (FVB) and B6 mice deficient for PECAM to identify the gene or genes responsible for this unique feature of B6 mice. We have identified a locus on murine chromosome 2 at approximately 35.8 Mb that is strongly associated (LOD score = 9.0) with inflammatory responses in the absence of PECAM. Conclusions/Significance: These data potentiate further study of the diapedesis machinery, as well as potential identification of new components of this machinery. As such, this study is an important step to better understanding the processes of inflammation

Evaluating rehabilitation following lumbar fusion surgery (REFS): study protocol for a randomised controlled trial

BACKGROUND: The rate of lumbar fusion surgery (LFS) is increasing. Clinical recovery often lags technical outcome. Approximately 40% of patients undergoing LFS rate themselves as symptomatically unchanged or worse following surgery. There is little research describing rehabilitation following LFS with no clear consensus as to what constitutes the optimum strategy. It is important to develop appropriate rehabilitation strategies to help patients manage pain and recover lost function following LFS. METHODS/DESIGN: The study design is a randomised controlled feasibility trial exploring the feasibility of providing a complex multi-method rehabilitation intervention 3 months following LFS. The rehabilitation protocol that we have developed involves small participant groups of therapist led structured education utilising principles of cognitive behavioral therapy (CBT), progressive, individualised exercise and peer support. Participants will be randomly allocated to either usual care (UC) or the rehabilitation group (RG). We will recruit 50 subjects, planning to undergo LFS, over 30 months. Following LFS all participants will experience normal care for the first 3 months. Subsequent to a satisfactory 3 month surgical review they will commence their allocated post-operative treatment (RG or UC). Data collection will occur at baseline (pre-operatively), 3, 6 and 12 months post-operatively. Primary outcomes will include an assessment of feasibility factors (including recruitment and compliance). Secondary outcomes will evaluate the acceptability and characteristics of a limited cluster of quantitative measures including the Oswestry Disability Index (ODI) and an aggregated assessment of physical function (walking 50 yards, ascend/descend a flight of stairs). A nested qualitative study will evaluate participants' experiences. DISCUSSION: This study will evaluate the feasibility of providing complex, structured rehabilitation in small groups 3 months following technically successful LFS. We will identify strengths and weakness of the proposed protocol and the usefulness and characteristics of the planned outcome measures. This will help shape the development of rehabilitation strategies and inform future work aimed at evaluating clinical efficacy. TRIAL REGISTRATION: ISRCTN60891364, 10/07/2014

A network perspective on the topological importance of enzymes and their phylogenetic conservation

<p>Abstract</p> <p>Background</p> <p>A metabolic network is the sum of all chemical transformations or reactions in the cell, with the metabolites being interconnected by enzyme-catalyzed reactions. Many enzymes exist in numerous species while others occur only in a few. We ask if there are relationships between the phylogenetic profile of an enzyme, or the number of different bacterial species that contain it, and its topological importance in the metabolic network. Our null hypothesis is that phylogenetic profile is independent of topological importance. To test our null hypothesis we constructed an enzyme network from the KEGG (Kyoto Encyclopedia of Genes and Genomes) database. We calculated three network indices of topological importance: the degree or the number of connections of a network node; closeness centrality, which measures how close a node is to others; and betweenness centrality measuring how frequently a node appears on all shortest paths between two other nodes.</p> <p>Results</p> <p>Enzyme phylogenetic profile correlates best with betweenness centrality and also quite closely with degree, but poorly with closeness centrality. Both betweenness and closeness centralities are non-local measures of topological importance and it is intriguing that they have contrasting power of predicting phylogenetic profile in bacterial species. We speculate that redundancy in an enzyme network may be reflected by betweenness centrality but not by closeness centrality. We also discuss factors influencing the correlation between phylogenetic profile and topological importance.</p> <p>Conclusion</p> <p>Our analysis falsifies the hypothesis that phylogenetic profile of enzymes is independent of enzyme network importance. Our results show that phylogenetic profile correlates better with degree and betweenness centrality, but less so with closeness centrality. Enzymes that occur in many bacterial species tend to be those that have high network importance. We speculate that this phenomenon originates in mechanisms driving network evolution. Closeness centrality reflects phylogenetic profile poorly. This is because metabolic networks often consist of distinct functional modules and some are not in the centre of the network. Enzymes in these peripheral parts of a network might be important for cell survival and should therefore occur in many bacterial species. They are, however, distant from other enzymes in the same network.</p