Total synthesis and biological evaluation of the tetramic acid based natural product harzianic acid and its stereoisomers

Financial support for this project was provided by Cancer Research UK (Grant No. C21383/A6950)The bioactive natural product harzianic acid was prepared for the first time in just six steps (longest linear sequence) with an overall yield of 22%. The identification of conditions to telescope amide bond formation and a Lacey-Dieckmann reaction into one pot proved important. The three stereoisomers of harzianic acid were also prepared, providing material for comparison of their biological activity. While all of the isomers promoted root growth, improved antifungal activity was unexpectedly associated with isomers in the enantiomeric series opposite that of harzianic acid.Publisher PDFPeer reviewe

Rapid, selective and stable HaloTag-Lb ADH immobilization directly from crude cell extract for the continuous biocatalytic production of chiral alcohols and epoxides

A strategy for biocatalyst immobilization in flow directly from the crude cell extract is described.EPSRC (Award Nos. EP/K009494/1 and EP/K039520/1), the German Federal Ministry of Education and Research (BMBF) within the project “Molecular Interaction Engineering” (funding code 031A095)

Efficacy of Oral Administration of Sodium Iodide to Prevent Bovine Respiratory Disease Complex

Background: The prevention of bovine respiratory disease complex (BRD) in beef cattle is important to maintaining health and productivity of calves in feeding operations. Objective: Determine whether BRD bacterial and viral pathogens are susceptible to the lactoperoxidase/hydrogen peroxide/ iodide (LPO/H2O2/I-) system in vitro and to determine whether the oral administration of sodium iodide (NaI) could achieve sufficient concentrations of iodine (I) in the respiratory secretions of weaned beef calves to inactivate these pathogens in vivo. Animals: Sixteen weaned, apparently healthy, commercial beef calves from the University of Missouri, College of Veterinary Medicine teaching herd. Methods: In vitro viral and bacterial assays were performed to determine susceptibility to the LPO/H2O2/I- system at varying concentrations of NaI. Sixteen randomly selected, healthy crossbred beef weanlings were administered 70 mg/kg NaI, or water, orally in a blinded, placebo-controlled trial. Blood and nasal secretions were collected for 72 hours and analyzed for I- concentration. Results: Bovine herpesvirus-1, parainfluenza-3, Mannheimia haemolytica and Bibersteinia trehalosi were all inactivated or inhibited in vitro by the LPO/H2O2/I- reaction. Oral administration of NaI caused a marked increase in nasal fluid I concentration with a Cmax = 181 (1,420 mM I), T12, a sufficient concentration to inactivate these pathogens in vitro. Conclusions and Clinical Importance: In vitro, the LPO/H2O2/I- system inactivates and inhibits common pathogens associated with BRD. The administration of oral NaI significantly increases the I concentration of nasal fluid indicating that this system might be useful in preventing bovine respiratory infections

Chronic venous leg ulcer care: Putting the patient at the heart of leg ulcer care Part 2: Development and evaluation of the consultation template

This is an accepted manuscript of an article published by MA Healthcare Ltd in British Journal of Community Nursing on 25/05/2018, available online: https://doi.org/10.12968/bjcn.2018.23.Sup6.S20 The accepted version of the publication may differ from the final published version.Part 2 in this article series summarises the final two phases of a study which explored the experiences of patients with leg ulcers and the impact of this condition on their quality of life. Early phases of the study revealed a mismatch between issues that affected a patient's quality of life and what they discussed during subsequent health care consultations. In light of this, a nominal group technique was employed to facilitate the development of a new leg ulcer consultation template with patient partners. The aim of this was to include many of the issues raised in phases 1. The new template was evaluated in terms of its utility, significance and clinical potential. The application of this template during routine consultations appears to encourage the patient to disclose issues that are important to them and may have otherwise been overlooked

Novel solvates M(BH4)3S(CH3)2 and properties of halide-free M(BH4)3 (M = Y or Gd)

Rare earth metal borohydrides have been proposed as materials for solid-state hydrogen storage because of their reasonably low temperature of decomposition. New synthesis methods, which provide halide-free yttrium and gadolinium borohydride, are presented using dimethyl sulfide and new solvates as intermediates. The solvates M(BH4)3S(CH3)2 (M = Y or Gd) are transformed to a-Y(BH4)3 or Gd(BH4)3 at ~140 °C as verified by thermal analysis. The monoclinic structure of Y(BH4)3S(CH3)2, space group P21/c, a = 5.52621(8), b = 22.3255(3), c = 8.0626(1) Å and ß = 100.408(1)°, is solved from synchrotron radiation powder X-ray diffraction data and consists of buckled layers of slightly distorted octahedrons of yttrium atoms coordinated to five borohydride groups and one dimethyl sulfide group. Significant hydrogen loss is observed from Y(BH4)3 below 300 °C and rehydrogenation at 300 °C and p(H2) = 1550 bar does not result in the reformation of Y(BH4)3, but instead yields YH3. Moreover, composites systems Y(BH4)3–LiBH4 1 : 1 and Y(BH4)3–LiCl 1 : 1 prepared from as-synthesised Y(BH4)3 are shown to melt at 190 and 220 °C, respectively

All-electron GW calculation based on the LAPW method: application to wurtzite ZnO

We present a new, all-electron implementation of the GW approximation and apply it to wurtzite ZnO. Eigenfunctions computed in the local-density approximation (LDA) by the full-potential linearized augmented-plane-wave (LAPW) or the linearized muffin-tin-orbital (LMTO) method supply the input for generating the Green function G and the screened Coulomb interaction W. A mixed basis is used for the expansion of W, consisting of plane waves in the interstitial region and augmented-wavefunction products in the augmentation-sphere regions. The frequency-dependence of the dielectric function is computed within the random-phase approximation (RPA), without a plasmon-pole approximation. The Zn 3d orbitals are treated as valence states within the LDA; both core and valence states are included in the self-energy calculation. The calculated bandgap is smaller than experiment by about 1eV, in contrast to previously reported GW results. Self-energy corrections are orbital-dependent, and push down the deep O 2s and Zn 3d levels by about 1eV relative to the LDA. The d level shifts closer to experiment but the size of shift is underestimated, suggesting that the RPA overscreens localized states.Comment: 10 pages, 3 figures, submitted to Phys. Rev.

An orthogonal biocatalytic approach for the safe generation and use of HCN in a multistep continuous preparation of chiral O-acetylcyanohydrins

An enantioselective preparation of O-acetylcyanohydrins has been accomplished by a three-step telescoped continuous process. The modular components enabled accurate control of two sequential biotransformations, safe handling of an in situ generated hazardous gas, and in-line stabilization of products. This method proved to be advantageous over the batch protocols in terms of reaction time (40 vs 345 min) and ease of operation, opening up access to reactions which have often been neglected due to safety concerns.We gratefully acknowledge the Deutsche Forschungsgemeinschaft (DFG) within the research training group GRK 1166 “Biocatalysis in non-conventional media (BioNoCo)”, and the EPSRC (Award Nos. EP/K009494/1 and EP/K039520/1)This is the final version of the article. It first appeared from Georg Thieme Verlag KG via http://dx.doi.org/10.1055/s-0035-156064

Asymmetric Fluid Criticality I: Scaling with Pressure Mixing

The thermodynamic behavior of a fluid near a vapor-liquid and, hence, asymmetric critical point is discussed within a general ``complete'' scaling theory incorporating pressure mixing in the nonlinear scaling fields as well as corrections to scaling. This theory allows for a Yang-Yang anomaly in which \mu_{\sigma}^{\prime\prime}(T), the second temperature derivative of the chemical potential along the phase boundary, diverges like the specific heat when T\to T_{\scriptsize c}; it also generates a leading singular term, |t|^{2\beta}, in the coexistence curve diameter, where t\equiv (T-T_{\scriptsize c}) /T_{\scriptsize c}. The behavior of various special loci, such as the critical isochore, the critical isotherm, the k-inflection loci, on which \chi^{(k)}\equiv \chi(\rho,T)/\rho^{k} (with \chi = \rho^{2} k_{\scriptsize B}TK_{T}) and C_{V}^{(k)}\equiv C_{V}(\rho,T)/\rho^{k} are maximal at fixed T, is carefully elucidated. These results are useful for analyzing simulations and experiments, since particular, nonuniversal values of k specify loci that approach the critical density most rapidly and reflect the pressure-mixing coefficient. Concrete illustrations are presented for the hard-core square-well fluid and for the restricted primitive model electrolyte. For comparison, a discussion of the classical (or Landau) theory is presented briefly and various interesting loci are determined explicitly and illustrated quantitatively for a van der Waals fluid.Comment: 21 pages in two-column format including 8 figure

Factors Associated with the Diversification of the Gut Microbial Communities within Chimpanzees from Gombe National Park.

The gastrointestinal tract harbors large and diverse populations of bacteria that vary among individuals and within individuals over time. Numerous internal and external factors can influence the contents of these microbial communities, including diet, geography, physiology, and the extent of contact among hosts. To investigate the contributions of such factors to the variation and changes in gut microbial communities, we analyzed the distal gut microbiota of individual chimpanzees from two communities in Gombe National Park, Tanzania. These samples, which were derived from 35 chimpanzees, many of whom have been monitored for multiple years, provide an unusually comprehensive longitudinal depth for individuals of known genetic relationships. Although the composition of the great-ape microbiota has been shown to codiversify with host species, indicating that host genetics and phylogeny have played a major role in its differentiation over evolutionary timescales, the geneaological relationships of individual chimpanzees did not coincide with the similarity in their gut microbial communities. However, the inhabitants from adjacent chimpanzee communities could be distinguished based on the contents of their gut microbiota. Despite the broad similarity of community members, as would be expected from shared diet or interactions, long-term immigrants to a community often harbored the most distinctive gut microbiota, suggesting that individuals retain hallmarks of their previous gut microbial communities for extended periods. This pattern was reinforced in several chimpanzees sampled over long temporal scales, in which the major constituents of the gut microbiota were maintained for nearly a decade