A High Cell‐Bearing Capacity Multibore Hollow Fiber Device for Macroencapsulation of Islets of Langerhans

Macroencapsulation of islets of Langerhans is a promising strategy for transplantation of insulin‐producing cells in the absence of immunosuppression to treat type 1 diabetes. Hollow fiber membranes are of interest there because they offer a large surface‐to‐volume ratio and can potentially be retrieved or refilled. However, current available fibers have limitations in exchange of nutrients, oxygen, and delivery of insulin potentially impacting graft survival. Here, multibore hollow fibers for islets encapsulation are designed and tested. They consist of seven bores and are prepared using nondegradable polymers with high mechanical stability and low cell adhesion properties. Human islets encapsulated there have a glucose induced insulin response (GIIS) similar to nonencapsulated islets. During 7 d of cell culture in vitro, the GIIS increases with graded doses of islets demonstrating the suitability of the microenvironment for islet survival. Moreover, first implantation studies in mice demonstrate device material biocompatibility with minimal tissue responses. Besides, formation of new blood vessels close to the implanted device is observed, an important requirement for maintaining islet viability and fast exchange of glucose and insulin. The results indicate that the developed fibers have high islet bearing capacity and can potentially be applied for a clinically applicable bioartificial pancreas.     

Lignin Biodegradation by a Cytochrome P450 Enzyme: A Computational Study into Syringol Activation by GcoA

A recently characterized cytochrome P450 isozyme GcoA activates lignin components through a selective O-demethylation or alternatively an acetal formation reaction. These are important reactions in biotechnology and, because lignin is readily available; it being the main component in plant cell walls. In this work we present a density functional theory study on a large active site model of GcoA to investigate syringol activation by an iron(IV)-oxo heme cation radical oxidant (Compound I) leading to hemiacetal and acetal products. Several substrate-binding positions were tested and full energy landscapes calculated. The study shows that substrate positioning determines the product distributions. Thus, with the phenol group pointing away from the heme, an O-demethylation is predicted, whereas an initial hydrogen-atom abstraction of the weak phenolic O-H group would trigger a pathway leading to ring-closure to form acetal products. Predictions on how to engineer P450 GcoA to get more selective product distributions are given.     

Cellular Fucosylation Inhibitors Based on Fluorinated Fucose-1-phosphates**

Fucosylation of glycans impacts a myriad of physiological and pathological processes. Inhibition of fucose expression emerges as a potential therapeutic avenue for example in cancer, inflammation, and infection. In this study, we found that protected 2-fluorofucose 1-phosphate efficiently inhibits cellular fucosylation with a four to seven times higher potency than known inhibitor 2FF, independently of the anomeric stereochemistry. Nucleotide sugar analysis revealed that both the α- and β-GDP-2FF anomers are formed inside the cell. In conclusion, we developed A2FF1P and B2FF1P as potent new tools for studying the role of fucosylation in health and disease and they are potential therapeutic candidates.     

Dramatic Influence of an Anionic Donor on the Oxygen‐Atom Transfer Reactivity of a MnV–Oxo Complex

Addition of an anionic donor to an Mn^V(O) porphyrinoid complex causes a dramatic increase in 2‐electron oxygen‐atom‐transfer (OAT) chemistry. The 6‐coordinate [Mn^V(O)(TBP₈Cz)(CN)]^? was generated from addition of Bu₄N⁺CN^? to the 5‐coordinate Mn^V(O) precursor. The cyanide‐ligated complex was characterized for the first time by Mn K‐edge X‐ray absorption spectroscopy (XAS) and gives Mn?O=1.53 Å, Mn?CN=2.21 Å. In combination with computational studies these distances were shown to correlate with a singlet ground state. Reaction of the CN^? complex with thioethers results in OAT to give the corresponding sulfoxide and a 2e^?‐reduced Mn^III(CN)^? complex. Kinetic measurements reveal a dramatic rate enhancement for OAT of approximately 24 000‐fold versus the same reaction for the parent 5‐coordinate complex. An Eyring analysis gives ΔH^≠=14 kcal mol^?1, ΔS^≠=?10 cal mol^?1 K^?1. Computational studies fully support the structures, spin states, and relative reactivity of the 5‐ and 6‐coordinate Mn^V(O) complexes.     

“Titration” polymerization of monovinylacetylene

A polymer consisting of a saturated carbon backbone with pendent acetylenic groups was prepared from monovinylacetylene. A titration was performed between the monomer and tertiary butyllithium, its lithiating agent. The charge transfer complex formed between the solvent THF and the tertiary butyllithium was used as an indicator of the unreacted butyllithium. Hence, a stoichiometric quantity of tertiary butyllithium was added dropwise to a solution of monovinylacetylene in THF to form lithiovinylacetylene. The addition of a slight excess of butyllithium led to the polymerization of the lithiated monomer. The obtained polymer was reprotonated and characterized. This polymerization was evaluated as a possible route to synthesize poly(vinylacetylene) with processable molecular weights, for its application as a potential carbon fiber precursor. © 1996 John Wiley & Sons, Inc.     

Reaction to Paul’s Column “Where do we find the graphs from PT programmes showing measurement performance?”

The tentative arguments mentioned by Paul De Bievre are discussed and alternatives are given that may lead to different insights.     

Riemannian geometry of irrotational vortex acoustics

We consider acoustic propagation in an irrotational vortex, using the technical machinery of differential geometry to investigate the "acoustic geometry" that is probed by the sound waves. The acoustic space-time curvature of a constant circulation hydrodynamical vortex leads to deflection of phonons at appreciable distances from the vortex core. The scattering angle for phonon rays is shown to be quadratic in the small quantity Gamma/2pi(cb), where Gamma is the vortex circulation, c the speed of sound, and b the impact parameter.     

Antigen-antibody interactions: binding studies with fluorescence and surface plasmon resonance exemplified by acid-traseolide as antigen

The interaction between the musk fragrance acid-traseolide and monoclonal antibodies (mAB) generated against this odorant has been investigated with two different techniques. Fluorescence spectroscopy was used to study the quenching of tryptophan fluorescence of the antibody upon binding acid-traseolide. This spectroscopic approach is based on measurements under equilibrium conditions. The second technique exploited the surface plasmon resonance (SPR) phenomenon. The acid-traseolide was immobilized in the surface matrix and upon presenting mAB changes in SPR were recorded in real time during the association reaction. The SPR approach can be considered as a kinetic method. Although having a different origin, both methods lead to comparable equilibrium dissociation constants (Kd). However, the results obtained with fluorescence spectroscopy were more accurate and reproducible. Not only the association of acid-traseolide with antibody was evaluated, also Fab fragment and peptide (H3-peptide) mimicking the heavy chain CDR3 of this antibody were included in this study. The Kd-values, determined by both methods, increase in the order mAB < Fab < H3-peptide because of diminishing recognition.