Influence of Dielectric Environment upon Isotope Effects onGlycoside Heterolysis: Computational Evaluation and AtomicHessian Analysis

Isotope effects depend upon the polarity of the bulk medium in which a chemical process occurs. Implicit solvent calculations with molecule-shaped cavities show that the equilibrium isotope effect (EIE) for heterolysis of the glycosidic bonds in 5′-methylthioadenosine and in 2-(p-nitrophenoxy)tetrahydropyran, both in water, are very sensitive in the range 2 ≤ ε ≤ 10 to the relative permittivity of the continuum surrounding the oxacarbenium ion. However, different implementations of nominally the same PCM method can lead to opposite trends being predicted for the same molecule. Computational modeling of the influence of the inhomogeneous effective dielectric surrounding a substrate within the protein environment of an enzymic reaction requires an explicit treatment. The EIE (KH/KD) for transfer of cyclopentyl, cyclohexyl, tetrahydrofuranyl and tetrahydropyranyl cations from water to cyclohexane is predicted by B3LYP/6-31+G(d) calculations with implicit solvation and confirmed by B3LYP/6-31+G(d)/OPLS-AA calculations with averaging over many explicit solvation configurations. Atomic Hessian analysis, whereby the full Hessian is reduced to the elements belonging to a single atom at the site of isotopic substitution, reveals a remarkable result for both implicit and explicit solvation: the influence of the solvent environment on these EIEs is essentially captured completely by only a 3 × 3 block of the Hessian, although these values must correctly reflect the influence of the whole environment. QM/MM simulation with ensemble averaging has an important role to play in assisting the meaningful interpretation of observed isotope effects for chemical reactions both in solution and catalyzed by enzymes

Impact of bidirectional relationships between streptococcus anginosus group and host tissue matrix components on cellular activity: Role in establishment of infection

This paper investigates pathogenic mechanisms of the Streptococcus anginosus group (SAG) of bacteria which influence the biological activity of periodontal ligament (PDL) cells, endothelial cells and also how matrix proteins produced by these host cells influence bacterial virulence factors. Isolates of SAG species, designated S. anginosus, S. constellatus and S. intermedius, were derived from healthy commensal and clinical pathogenic infection sites. SAG culture supernatants contained multiple protein components which differed between isolates. All SAG supernatants increased cellular proliferation and decreased decorin synthesis and collagen assembly by PDL cells and reduced endothelial cell migration. SAG isolates responded differently to extracellular matrix (ECM) components synthesised by PDL cells, but there was an overall notable increase in hydrolytic enzyme activity and in the production of the cytotoxin intermedilysin by S. intermedius. Collectively, the results indicate that both commensal and pathogenic SAG isolates were capable of impairing the ability of PDL cells and endothelial cells to make functional vascularised tissue. Reduced decorin synthesis is likely to have a major impact on cell signalling, angiogenesis and matrix assembly. Furthermore, ECM components produced by PDL cells were differentially capable of moderately increasing SAG enzymic activity, leading to subtle ECM modifications. The impact this bidirectional effect has on the tissue remodelling process is discussed

Different types of soluble fermentable dietary fibre decrease food intake, body weight gain and adiposity in young adult male rats

We thank Donna Wallace and the Rowett Animal House staff for the daily care of experimental rats, body weight and food intake measurements and MRI scanning, Vivien Buchan and Donna Henderson of the Rowett Analytical Department for proximate analyses and SCFA GC, and Andrew Chappell for conducting the beta-glucan analysis. This research was funded by the Scottish Government’s Rural and Environment Science and Analytical Services Division.Peer reviewedPublisher PD

Simultaneous differential scanning calorimetry – synchrotron X-ray powder diffraction : a powerful technique for physical form characterisation in pharmaceutical materials

© 2016 American Chemical Society. We report a powerful new technique: hyphenating synchrotron X-ray powder diffraction (XRD) with differential scanning calorimetry (DSC). This is achieved with a simple modification to a standard laboratory DSC instrument, in contrast to previous reports which have involved extensive and complex modifications to a DSC to mount it in the synchrotron beam. The high-energy X-rays of the synchrotron permit the recording of powder diffraction patterns in as little as 2 s, meaning that thermally induced phase changes can be accurately quantified and additional insight on the nature of phase transitions obtained. Such detailed knowledge cannot be gained from existing laboratory XRD instruments, since much longer collection times are required. We demonstrate the power of our approach with two model systems, glutaric acid and sulfathiazole, both of which show enantiotropic polymorphism. The phase transformations between the low and high temperature polymorphs are revealed to be direct solid-solid processes, and sequential refinement against the diffraction patterns obtained permits phase fractions at each temperature to be calculated and unit cell parameters to be accurately quantified as a function of temperature. The combination of XRD and DSC has further allowed us to identify mixtures of phases which appeared phase-pure by DSC

Nonlinear Breathing-like Localized Modes in C60 Nanocrystals

We study the dynamics of nanocrystals composed of C60 fullerene molecules. We demonstrate that such structures can support long-lived strongly localized nonlinear oscillatory modes, which resemble discrete breathers in simple lattices. We reveal that at room temperatures the lifetime of such nonlinear localized modes may exceed tens of picoseconds; this suggests that C60 nanoclusters should demonstrate anomalously slow thermal relaxation when the temperature gradient decays in accord to a power law, thus violating the Cattaneo-Vernotte law of thermal conductivity.Comment: 6 pages, 6 figure

Enantioselective Intermolecular C-H Amination Directed by a Chiral Cation.

The enantioselective amination of C(sp3)-H bonds is a powerful synthetic transformation yet highly challenging to achieve in an intermolecular sense. We have developed a family of anionic variants of the best-in-class catalyst for Rh-catalyzed C-H amination, Rh2(esp)2, with which we have associated chiral cations derived from quaternized cinchona alkaloids. These ion-paired catalysts enable high levels of enantioselectivity to be achieved in the benzylic C-H amination of substrates bearing pendant hydroxyl groups. Additionally, the quinoline of the chiral cation appears to engage in axial ligation to the rhodium complex, providing improved yields of product versus Rh2(esp)2 and highlighting the dual role that the cation is playing. These results underline the potential of using chiral cations to control enantioselectivity in challenging transition-metal-catalyzed transformations

Detection limits of organic compounds achievable with intense, short-pulse lasers

Many organic molecules have strong absorption bands which can be accessed by ultraviolet short pulse lasers to produce efficient ionization. This resonant multiphoton ionization scheme has already been exploited as an ionization source in time-of-flight mass spectrometers used for environmental trace analysis. In the present work we quantify the ultimate potential of this technique by measuring absolute ion yields produced from the interaction of 267 nm femtosecond laser pulses with the organic molecules indole and toluene, and gases Xe, N2 and O2. Using multiphoton ionization cross sections extracted from these results, we show that the laser pulse parameters required for real-time detection of aromatic molecules at concentrations of one part per trillion in air and a limit of detection of a few attomoles are achievable with presently available commercial laser systems. The potential applications for the analysis of human breath, blood and tissue samples are discussed

Intra-session and inter-day reliability of the Myon 320 electromyography system during sub-maximal contractions

Electromyography systems are widely used within the field of scientific and clinical practices. The reliability of these systems are paramount when conducting research. The reliability of Myon 320 Surface Electromyography System is yet to be determined. This study aims to determine the intra-session and inter-day reliability of the Myon 320 Surface Electromyography System. Muscle activity from fifteen participants was measured at the anterior deltoid muscle during a bilateral front raise exercise, the vastus lateralis muscle during a squat exercise and the extensor carpi radialis brevis (ECRB) muscle during an isometric handgrip task. Intra-session and inter-day reliability was calculated by intraclass correlation coefficient, standard error of measurement and coefficient of variation (CV). The normalized root mean squared (RMS) surface electromyographic signals produced good intra-session and inter-day testing intraclass correlation coefficient values (range: 0.63-0.97) together with low standard error of measurement (range: 1.49-2.32) and CV (range: 95% Confidence Interval = 0.36-12.71) measures for the dynamic-and-isometric contractions. The findings indicate that the Myon 320 Surface Electromyography System produces good to fair reliability when examining intra-session and inter-day reliability. Findings of the study provide evidence of the reliability of electromyography between trials which is essential during clinical testing.</p

Diffuse Gastric Ganglioneuromatosis: Novel Presentation of PTEN

Gastrointestinal ganglioneuromatous proliferations are rare, most often found in the colon, and are three types: polypoid ganglioneuromas, ganglioneuromatous polyposis, and diffuse ganglioneuromatosis. We present a case of diffuse ganglioneuromatosis in the posterior gastric wall in a nine-year-old female. To our knowledge, this is the first reported case of diffuse ganglioneuromatosis located in the stomach. Only six cases of gastric ganglioneuromatous proliferations have previously been reported, two in English and none were diffuse ganglioneuromatosis. A diagnosis of diffuse ganglioneuromatosis is relevant for patient care because, unlike sporadic polypoid ganglioneuromas or ganglioneuromatous polyposis, most are syndromic. Diffuse ganglioneuromatosis is commonly associated with neurofibromatosis type 1, multiple endocrine neoplasia type 2b, and Cowden Syndrome, one of the phenotypes of PTEN hamartoma tumor syndrome. The patient had the noted gastric diffuse ganglioneuromatosis, as well as other major and minor criteria for Cowden syndrome. Genetic testing revealed a novel frameshift mutation in the PTEN gene in the patient, her father, paternal aunt, and the aunt’s son who is a paternal first cousin of the patient